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Wang J, Yang L, Sun P, Guo C, Jin Y, Jing X. Expression patterns of serum miR-27a-3p and activating transcription factor 3 in children with bronchial asthma and their correlations with airway inflammation. THE CLINICAL RESPIRATORY JOURNAL 2025; 19:e13631. [PMID: 37385291 PMCID: PMC11931318 DOI: 10.1111/crj.13631] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/21/2022] [Revised: 03/30/2023] [Accepted: 05/05/2023] [Indexed: 07/01/2023]
Abstract
INTRODUCTION Bronchial asthma (BA) is a heterogeneous disease characterized by chronic airway inflammation. This study investigated the serum miR-27a-3p/activating transcription factor 3 (ATF3) expression in children with BA and their correlations with airway inflammation. METHODS Children with BA (N = 120) and healthy children (N = 108) were enrolled. Serum levels of interleukin (IL)-17, IL-6, tumor necrosis factor (TNF)-α, immunoglobulin E (IgE), miR-27a-3p, ATF3, and the number of eosinophils (EOS) were measured using enzyme-linked immunosorbent assay (ELISA), reverse transcription quantitative polymerase chain reaction (RT-qPCR), and an automatic hematology analyzer. The correlations between miR-27a-3p and ATF3 and between miR-27a-3p/ATF3 and inflammation-related factors were analyzed by the Pearson method. The diagnostic values of miR-27a-3p and ATF3 in BA were evaluated using receiver operating characteristic (ROC) curves. The influencing factors of BA were assessed using multivariate logistic regression. Finally, the targeting relation between miR-27a-3p and ATF3 was predicted and analyzed by TargetScan and Starbase databases, and dual-luciferase assay. RESULTS There were significant differences in forced expiratory volume in 1 s (FEV1)% predicted and FEV1/forced vital capacity (FVC)%, serum levels of IgE, IL-17, IL-6, and TNF-α, and EOS numbers between healthy children and BA children. Serum miR-27a-3p was negatively correlated with ATF3 and positively correlated with inflammation-related factors in BA children. Serum ATF3 mRNA levels were negatively correlated with inflammatory factors in BA children. miR-27a-3p and ATF3 had good diagnostic values in BA children. FEV% predicted, IL-6, TNF-α, miR-27a-3p, and ATF3 were independent risk factors for BA. miR-27a-3p targeted ATF3. CONCLUSION Serum miR-27a-3p was highly expressed, whereas ATF3 was poorly expressed in BA children, and they were significantly correlated with airway inflammation, had good diagnostic values in BA children, and were independent risk factors for asthma.
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Affiliation(s)
- Jingcai Wang
- Department of PediatricThe Affiliated Hospital of Chengde Medical UniversityChengdeHebeiChina
| | - Lixin Yang
- Department of PediatricThe Affiliated Hospital of Chengde Medical UniversityChengdeHebeiChina
| | - Peng Sun
- Department of PediatricThe Affiliated Hospital of Chengde Medical UniversityChengdeHebeiChina
| | - Chunyan Guo
- Department of PediatricThe Affiliated Hospital of Chengde Medical UniversityChengdeHebeiChina
| | - Yuzi Jin
- Department of PediatricThe Affiliated Hospital of Chengde Medical UniversityChengdeHebeiChina
| | - Xiaoqing Jing
- Department of PediatricThe Affiliated Hospital of Chengde Medical UniversityChengdeHebeiChina
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Kiełbowski K, Jędrasiak A, Bakinowska E, Pawlik A. The Role of Long Non-Coding RNA in the Pathogenesis of Psoriasis. Noncoding RNA 2025; 11:7. [PMID: 39846685 PMCID: PMC11755624 DOI: 10.3390/ncrna11010007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2024] [Revised: 01/04/2025] [Accepted: 01/14/2025] [Indexed: 01/24/2025] Open
Abstract
Psoriasis is a chronic immune-mediated disease with complex pathogenesis. The altered proliferation and differentiation of keratinocytes, together with the activity of dendritic cells and T cells, are crucial drivers of psoriasis progression. Long non-coding RNAs (lncRNAs) are composed of over 200 nucleotides and exert a large variety of functions, including the regulation of gene expression. Under pathological conditions, the expression of lncRNAs is frequently dysregulated. Recent studies demonstrated that lncRNAs significantly affect major cellular processes, and their aberrant expression is likely involved in the pathogenesis of various disorders. In this review, we will discuss the role of lncRNAs in the pathophysiology of psoriasis. We will summarize recent studies that investigated the relationships between lncRNAs and keratinocyte proliferation and pro-inflammatory responses.
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Affiliation(s)
- Kajetan Kiełbowski
- Department of Physiology, Pomeranian Medical University, 70-111 Szczecin, Poland; (A.J.); (E.B.)
| | | | | | - Andrzej Pawlik
- Department of Physiology, Pomeranian Medical University, 70-111 Szczecin, Poland; (A.J.); (E.B.)
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Xu X, Yin J, Yang Y, Liu H, Yu J, Luo X, Zhang Y, Song X. Advances in co-pathogenesis of the united airway diseases. Respir Med 2024; 225:107580. [PMID: 38484897 DOI: 10.1016/j.rmed.2024.107580] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2023] [Revised: 02/02/2024] [Accepted: 02/22/2024] [Indexed: 03/19/2024]
Abstract
According to the concept of "united airway diseases", the airway is a single organ in which upper and lower airway diseases are commonly comorbid. A range of inflammatory factors have been found to play an important role in the chain reaction of upper and lower airway diseases. However, the amount of research on this concept remains limited. The underlying mechanism of the relationship between typical diseases of the united airway, such as asthma, allergic rhinitis, and chronic sinusitis, also needs to be further explored. This review highlights the interaction between upper and lower respiratory diseases gathered from epidemiological, histoembryology, neural mechanistic, microbiological, and clinical studies, revealing the relationship between the upper and lower respiratory tracts.
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Affiliation(s)
- Xinjun Xu
- Department of Otolaryngology, Head and Neck Surgery. Yantai Yuhuangding Hospital, Qingdao University, Yantai, China; Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases, Yantai, China
| | - Jiali Yin
- Department of Otolaryngology, Head and Neck Surgery. Yantai Yuhuangding Hospital, Qingdao University, Yantai, China; Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases, Yantai, China
| | - Yujuan Yang
- Department of Otolaryngology, Head and Neck Surgery. Yantai Yuhuangding Hospital, Qingdao University, Yantai, China; Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases, Yantai, China
| | - Huifang Liu
- Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases, Yantai, China; The 2nd School of Clinical Medicine of Binzhou Medical University, Yantai, Shandong, China
| | - Jingyi Yu
- Department of Otolaryngology, Head and Neck Surgery. Yantai Yuhuangding Hospital, Qingdao University, Yantai, China; Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases, Yantai, China
| | - Xianghuang Luo
- Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases, Yantai, China; School of Clinical Medicine, Weifang Medical University, Weifang, 261042, China
| | - Yu Zhang
- Department of Otolaryngology, Head and Neck Surgery. Yantai Yuhuangding Hospital, Qingdao University, Yantai, China; Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases, Yantai, China.
| | - Xicheng Song
- Department of Otolaryngology, Head and Neck Surgery. Yantai Yuhuangding Hospital, Qingdao University, Yantai, China; Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases, Yantai, China.
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4
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Zhang M, Han Y. MicroRNAs in chronic pediatric diseases (Review). Exp Ther Med 2024; 27:100. [PMID: 38356668 PMCID: PMC10865459 DOI: 10.3892/etm.2024.12388] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2023] [Accepted: 12/15/2023] [Indexed: 02/16/2024] Open
Abstract
MicroRNAs are small non-coding RNAs with a length of 20-24 nucleotides. They bind to the 3'-untranslated region of target genes to induce the degradation of target mRNAs or inhibit their translation. Therefore, they are involved in the regulation of development, apoptosis, proliferation, differentiation and other biological processes (including hormone secretion, signaling and viral infections). Chronic diseases in children may be difficult to treat and are often associated with malnutrition resulting from a poor diet. Consequently, further complications, disease aggravation and increased treatment costs impose a burden on patients and their families. Existing evidence suggests that microRNAs are involved in various chronic non-neoplastic diseases in children. The present review discusses the roles of microRNAs in five major chronic diseases in children, namely, diabetes mellitus, congenital heart diseases, liver diseases, bronchial asthma and epilepsy, providing a theoretical basis for them to become therapeutic biomarkers in chronic pediatric diseases.
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Affiliation(s)
- Mingyao Zhang
- Department of Pediatrics, The Third Affiliated Hospital of Changchun University of Chinese Medicine, Changchun, Jilin 130117, P.R. China
| | - Yanhua Han
- Department of Pediatrics, Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, Jilin 130021, P.R. China
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Alharbi KS. The ncRNA-TGF-β axis: Unveiling new frontiers in colorectal cancer research. Pathol Res Pract 2024; 254:155138. [PMID: 38266458 DOI: 10.1016/j.prp.2024.155138] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2023] [Revised: 01/07/2024] [Accepted: 01/11/2024] [Indexed: 01/26/2024]
Abstract
Colorectal cancer (CRC) poses a substantial global challenge, necessitating a deeper understanding of the molecular underpinnings governing its onset and progression. The transforming growth factor beta (TGF-β) network has been a well-recognized cornerstone in advancing CRC. Nevertheless, a recent study has highlighted the growing importance of non-coding RNAs (ncRNAs) in this context. This comprehensive review aims to present an extensive examination of the interaction between ncRNAs and TGF-signaling. Noncoding RNAs (ncRNAs), encompassing circular RNAs (circRNAs), long-ncRNAs (lncRNAs), and microRNAs (miRNAs), have surfaced as pivotal modulators governing various aspects of TGF-β signaling. MiRNAs have been discovered to target elements within the TGF-β signaling, either enhancing or inhibiting signaling, depending on the context. LncRNAs have been associated with CRC progression, functioning as miRNA sponges or directly influencing TGF-β pathway elements. Even circRNAs, a relatively recent addition to the ncRNA family, have impacted CRC, affecting TGF-β signaling through diverse mechanisms. This review encompasses recent progress in comprehending specific ncRNAs involved in TGF-β signaling, their functional roles, and their clinical relevance in CRC. We investigate the possibility of ncRNAs as targets for detection, prognosis, and therapy. Additionally, we explore the interaction of TGF-β and other pathways in CRC and the role of ncRNAs within this intricate network. As we unveil the intricate regulatory function of ncRNAs in the TGF-β signaling in CRC, we gain valuable insights into the disease's pathogenesis. Incorporating these discoveries into clinical settings holds promise for more precise diagnosis, prognosis, and targeted therapeutic approaches, ultimately enhancing the care of CRC patients. This comprehensive review underscores the ever-evolving landscape of ncRNA research in CRC and the potential for novel interventions in the battle against this formidable disease.
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Affiliation(s)
- Khalid Saad Alharbi
- Department of Pharmacology and Toxicology, Unaizah College of Pharmacy, Qassim University, Qassim 51452, Saudi Arabia.
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Zhou H, Xu JL, Huang SX, He Y, He XW, Lu S, Yao B. Hepatic vagotomy blunts liver regeneration after hepatectomy by downregulating the expression of interleukin-22. World J Gastrointest Surg 2023; 15:2866-2878. [PMID: 38222006 PMCID: PMC10784834 DOI: 10.4240/wjgs.v15.i12.2866] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2023] [Revised: 11/01/2023] [Accepted: 11/17/2023] [Indexed: 12/27/2023] Open
Abstract
BACKGROUND Rapid regeneration of the residual liver is one of the key determinants of successful partial hepatectomy (PHx). At present, there is a lack of recognized safe, effective, and stable drugs to promote liver regeneration. It has been reported that vagus nerve signaling is beneficial to liver regeneration, but the potential mechanism at play here is not fully understood. AIM To explore the effect and mechanism of hepatic vagus nerve in liver regeneration after PHx. METHODS A PHx plus hepatic vagotomy (Hv) mouse model was established. The effect of Hv on liver regeneration after PHx was determined by comparing the liver regeneration levels of the PHx-Hv group and the PHx-sham group mice. In order to further investigate the role of interleukin (IL)-22 in liver regeneration inhibition mediated by Hv, the levels of IL-22 in the PHx-Hv group and the PHx-sham group was measured. The degree of liver injury in the PHx-Hv group and the PHx-sham group mice was detected to determine the role of the hepatic vagus nerve in liver injury after PHx. RESULTS Compared to control-group mice, Hv mice showed severe liver injury and weakened liver regeneration after PHx. Further research found that Hv downregulates the production of IL-22 induced by PHx and blocks activation of the signal transducer and activator of transcription 3 (STAT3) pathway then reduces the expression of various mitogenic and anti-apoptotic proteins after PHx. Exogenous IL-22 reverses the inhibition of liver regeneration induced by Hv and alleviates liver injury, while treatment with IL-22 binding protein (an inhibitor of IL-22 signaling) reduce the concentration of IL-22 induced by PHx, inhibits the activation of the STAT3 signaling pathway in the liver after PHx, thereby hindering liver regeneration and aggravating liver injury in PHx-sham mice. CONCLUSION Hv attenuates liver regeneration after hepatectomy, and the mechanism may be related to the fact that Hv downregulates the production of IL-22, then blocks activation of the STAT3 pathway.
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Affiliation(s)
- Heng Zhou
- Department of Pharmacy, The First People’s Hospital of Huzhou, First Affiliated Hospital of Huzhou University, Huzhou 313000, Zhejiang Province, China
| | - Ju-Ling Xu
- Department of Medicine, Medical School of Huzhou University, Huzhou 313000, Zhejiang Province, China
| | - San-Xiong Huang
- Department of Hepatobiliary Surgery, The First People’s Hospital of Huzhou, Huzhou 313000, Zhejiang Province, China
| | - Ying He
- Zhejiang Provincial Key Laboratory of Media Biology and Pathogenic Control, Central Laboratory, First Affiliated Hospital of Huzhou University, Huzhou 313000, Zhejiang Province, China
| | - Xiao-Wei He
- Department of Pharmacy, The First People’s Hospital of Huzhou, First Affiliated Hospital of Huzhou University, Huzhou 313000, Zhejiang Province, China
| | - Sheng Lu
- Department of Pharmacy, The First People’s Hospital of Huzhou, First Affiliated Hospital of Huzhou University, Huzhou 313000, Zhejiang Province, China
| | - Bin Yao
- Department of Pharmacy, The First People’s Hospital of Huzhou, First Affiliated Hospital of Huzhou University, Huzhou 313000, Zhejiang Province, China
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Zhu Z, Freishtat RJ, Harmon B, Hahn A, Teach SJ, Pérez-Losada M, Hasegawa K, Camargo CA. Nasal airway microRNA profiling of infants with severe bronchiolitis and risk of childhood asthma: a multicentre prospective study. Eur Respir J 2023; 62:2300502. [PMID: 37321621 PMCID: PMC10578345 DOI: 10.1183/13993003.00502-2023] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2023] [Accepted: 05/31/2023] [Indexed: 06/17/2023]
Abstract
BACKGROUND Severe bronchiolitis (i.e. bronchiolitis requiring hospitalisation) during infancy is a major risk factor for childhood asthma. However, the exact mechanism linking these common conditions remains unclear. We examined the longitudinal relationship between nasal airway miRNAs during severe bronchiolitis and the risk of developing asthma. METHODS In a 17-centre prospective cohort study of infants with severe bronchiolitis, we sequenced their nasal microRNA at hospitalisation. First, we identified differentially expressed microRNAs (DEmiRNAs) associated with the risk of developing asthma by age 6 years. Second, we characterised the DEmiRNAs based on their association with asthma-related clinical features, and expression level by tissue and cell types. Third, we conducted pathway and network analyses by integrating DEmiRNAs and their mRNA targets. Finally, we investigated the association of DEmiRNAs and nasal cytokines. RESULTS In 575 infants (median age 3 months), we identified 23 DEmiRNAs associated with asthma development (e.g. hsa-miR-29a-3p; false discovery rate (FDR) <0.10), particularly in infants with respiratory syncytial virus infection (FDR for the interaction <0.05). These DEmiRNAs were associated with 16 asthma-related clinical features (FDR <0.05), e.g. infant eczema and corticosteroid use during hospitalisation. In addition, these DEmiRNAs were highly expressed in lung tissue and immune cells (e.g. T-helper cells, neutrophils). Third, DEmiRNAs were negatively correlated with their mRNA targets (e.g. hsa-miR-324-3p/IL13), which were enriched in asthma-related pathways (FDR <0.05), e.g. toll-like receptor, PI3K-Akt and FcɛR signalling pathways, and validated by cytokine data. CONCLUSION In a multicentre cohort of infants with severe bronchiolitis, we identified nasal miRNAs during illness that were associated with major asthma-related clinical features, immune response, and risk of asthma development.
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Affiliation(s)
- Zhaozhong Zhu
- Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Robert J Freishtat
- Center for Genetic Medicine Research, Children's National Hospital, Washington, DC, USA
- Division of Emergency Medicine, Children's National Hospital, Washington, DC, USA
- Department of Pediatrics, George Washington University School of Medicine and Health Sciences, Washington, DC, USA
| | - Brennan Harmon
- Center for Genetic Medicine Research, Children's National Hospital, Washington, DC, USA
| | - Andrea Hahn
- Center for Genetic Medicine Research, Children's National Hospital, Washington, DC, USA
- Department of Pediatrics, George Washington University School of Medicine and Health Sciences, Washington, DC, USA
- Division of Infectious Diseases, Children's National Hospital, Washington, DC, USA
| | - Stephen J Teach
- Division of Emergency Medicine, Children's National Hospital, Washington, DC, USA
- Department of Pediatrics, George Washington University School of Medicine and Health Sciences, Washington, DC, USA
| | - Marcos Pérez-Losada
- Computational Biology Institute, Department of Biostatistics and Bioinformatics, The George Washington University, Washington, DC, USA
| | - Kohei Hasegawa
- Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Carlos A Camargo
- Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
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Lee YS, Lee YS. nc886, an RNA Polymerase III-Transcribed Noncoding RNA Whose Expression Is Dynamic and Regulated by Intriguing Mechanisms. Int J Mol Sci 2023; 24:ijms24108533. [PMID: 37239877 DOI: 10.3390/ijms24108533] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Revised: 04/28/2023] [Accepted: 05/08/2023] [Indexed: 05/28/2023] Open
Abstract
nc886 is a medium-sized non-coding RNA that is transcribed by RNA polymerase III (Pol III) and plays diverse roles in tumorigenesis, innate immunity, and other cellular processes. Although Pol III-transcribed ncRNAs were previously thought to be expressed constitutively, this concept is evolving, and nc886 is the most notable example. The transcription of nc886 in a cell, as well as in human individuals, is controlled by multiple mechanisms, including its promoter CpG DNA methylation and transcription factor activity. Additionally, the RNA instability of nc886 contributes to its highly variable steady-state expression levels in a given situation. This comprehensive review discusses nc886's variable expression in physiological and pathological conditions and critically examines the regulatory factors that determine its expression levels.
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Affiliation(s)
- Yeon-Su Lee
- Rare Cancer Branch, Research Institute, National Cancer Center, Goyang 10408, Republic of Korea
| | - Yong Sun Lee
- Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang 10408, Republic of Korea
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Studies on the role of non-coding RNAs in controlling the activity of T cells in asthma. Noncoding RNA Res 2023; 8:211-217. [PMID: 36865391 PMCID: PMC9972402 DOI: 10.1016/j.ncrna.2023.02.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2023] [Revised: 02/13/2023] [Accepted: 02/13/2023] [Indexed: 02/17/2023] Open
Abstract
Bronchial asthma, commonly known as asthma, is a chronic inflammatory disease characterized by airway inflammation, increased responsiveness and changes in airway structure. T cells, particularly T helper cells, play a crucial role in the disease. Non-coding RNAs, which are RNAs that do not code for proteins, mainly include microRNAs, long non-coding RNAs, and circular RNAs, play a role in regulating various biological processes. Studies have shown that non-coding RNAs have an important role in the activation and transformation of T cells and other biological processes in asthma. The specific mechanisms and clinical applications are worth further examination. This article reviews the recent research on the role of microRNAs, long non-coding RNAs and circular RNAs in T cells in asthma.
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Maggi E, Parronchi P, Azzarone BG, Moretta L. A pathogenic integrated view explaining the different endotypes of asthma and allergic disorders. Allergy 2022; 77:3267-3292. [PMID: 35842745 DOI: 10.1111/all.15445] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Revised: 07/08/2022] [Accepted: 07/13/2022] [Indexed: 01/28/2023]
Abstract
The inflammation of allergic diseases is characterized by a complex interaction between type 2 and type 3 immune responses, explaining clinical symptoms and histopathological patterns. Airborne stimuli activate the mucosal epithelium to release a number of molecules impacting the activity of resident immune and environmental cells. Signals from the mucosal barrier, regulatory cells, and the inflamed tissue are crucial conditions able to modify innate and adaptive effector cells providing the selective homing of eosinophils or neutrophils. The high plasticity of resident T- and innate lymphoid cells responding to external signals is the prerequisite to explain the multiplicity of endotypes of allergic diseases. This notion paved the way for the huge use of specific biologic drugs interfering with pathogenic mechanisms of inflammation. Based on the response of the epithelial barrier, the activity of resident regulatory cells, and functions of structural non-lymphoid environmental cells, this review proposes some immunopathogenic scenarios characterizing the principal endotypes which can be associated with a precise phenotype of asthma. Recent literature indicates that similar concepts can also be applied to the inflammation of other non-respiratory allergic disorders. The next challenges will consist in defining specific biomarker(s) of each endotype allowing for a quick diagnosis and the most effective personalized therapy.
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Affiliation(s)
- Enrico Maggi
- Department of Immunology, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | - Paola Parronchi
- Department of Clinical and Experimental Medicine, University of Florence, Florence, Italy
| | | | - Lorenzo Moretta
- Department of Immunology, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
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11
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Mirra D, Cione E, Spaziano G, Esposito R, Sorgenti M, Granato E, Cerqua I, Muraca L, Iovino P, Gallelli L, D’Agostino B. Circulating MicroRNAs Expression Profile in Lung Inflammation: A Preliminary Study. J Clin Med 2022; 11:jcm11185446. [PMID: 36143090 PMCID: PMC9500709 DOI: 10.3390/jcm11185446] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2022] [Revised: 09/08/2022] [Accepted: 09/12/2022] [Indexed: 11/29/2022] Open
Abstract
Background: Bronchial asthma is an inflammatory airway disease with an ever-increasing incidence. Therefore, innovative management strategies are urgently needed. MicroRNAs are small molecules that play a key role in lungs cellular functions and are involved in chronic inflammatory diseases, such as bronchial asthma. This study aims to compare microRNA serum expression between subjects with asthma, obesity, the most common co-morbidity in asthma, and healthy controls to obtain a specific expression profile specifically related to lung inflammation. Methods: We collected serum samples from a prospective cohort of 25 sex-matched subjects to determine circulating miRNAs through a quantitative RT-PCR. Moreover, we performed an in silico prediction of microRNA target genes linked to lung inflammation. Results: Asthmatic patients had a significant lower expression of hsa-miR-34a-5p, 181a-5p and 146a-5p compared to both obese and healthy ones suggesting microRNAs’ specific involvement in the regulation of lungs inflammatory response. Indeed, using in silico analysis, we identified microRNAs novel target genes as GATA family, linked to the inflammatory-related pathway. Conclusions: This study identifies a novel circulating miRNAs expression profile with promising potentials for asthma clinical evaluations and management. Further and larger investigations will be needed to confirm the potential role of microRNA as a clinical marker of bronchial asthma and eventually of pharmacological treatment response.
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Affiliation(s)
- Davida Mirra
- Department of Environmental Biological and Pharmaceutical Sciences and Technologies University of Campania “Luigi Vanvitelli”, 81100 Caserta, Italy
| | - Erika Cione
- Department of Pharmacy, Health and Nutritional Sciences-Department of Excellence 2018–2022, University of Calabria, 87036 Rende, CS, Italy
| | - Giuseppe Spaziano
- Department of Environmental Biological and Pharmaceutical Sciences and Technologies University of Campania “Luigi Vanvitelli”, 81100 Caserta, Italy
| | - Renata Esposito
- Department of Environmental Biological and Pharmaceutical Sciences and Technologies University of Campania “Luigi Vanvitelli”, 81100 Caserta, Italy
| | - Mario Sorgenti
- Respiratory Diseases in Primary Care, ASP Catanzaro, 88100 Catanzaro, Italy
| | - Elisabetta Granato
- Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, 80138 Naples, Italy
| | - Ida Cerqua
- Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, 80138 Naples, Italy
| | - Lucia Muraca
- Department of Primary Care, ASP Catanzaro, 88100 Catanzaro, Italy
| | - Pasquale Iovino
- Department of Environmental Biological and Pharmaceutical Sciences and Technologies University of Campania “Luigi Vanvitelli”, 81100 Caserta, Italy
| | - Luca Gallelli
- Clinical Pharmacology and Pharmacovigilance Unit, Department of Health Sciences, Mater Domini Hospital, University of Catanzaro, 88100 Catanzaro, Italy
- Correspondence:
| | - Bruno D’Agostino
- Department of Environmental Biological and Pharmaceutical Sciences and Technologies University of Campania “Luigi Vanvitelli”, 81100 Caserta, Italy
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Farmanzadeh A, Qujeq D, Yousefi T. The Interaction Network of MicroRNAs with Cytokines and Signaling Pathways in Allergic Asthma. Microrna 2022; 11:104-117. [PMID: 35507792 DOI: 10.2174/2211536611666220428134324] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2021] [Revised: 01/15/2022] [Accepted: 03/10/2022] [Indexed: 01/01/2023]
Abstract
Allergic asthma is a complicated disease that is affected by many factors. Numerous cytokines and signaling pathways are attributed to the cause of asthma symptoms. MicroRNAs (miRNAs) are a group of small non-coding single-stranded RNA molecules that are involved in gene silencing and posttranscriptional regulation of gene expression by targeting mRNAs. In pathological conditions, altered expression of microRNAs differentially regulates cytokines and signaling pathways and therefore, can be the underlying reason for the pathogenesis of allergic asthma. Indeed, microRNAs participate in airway inflammation via inducing airway structural cells and activating immune responses by targeting cytokines and signaling pathways. Thus, to make a complete understanding of allergic asthma, it is necessary to investigate the communication network of microRNAs with cytokines and signaling pathways which is contributed to the pathogenesis of allergic asthma. Here, we shed light on this aspect of asthma pathology by Summarizing our current knowledge of this topic.
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Affiliation(s)
- Ali Farmanzadeh
- Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran
| | - Durdi Qujeq
- Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran.,Department of Clinical Biochemistry, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran
| | - Tooba Yousefi
- Department of Clinical Biochemistry, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran
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de Sousa TR, Fagundes BO, Nascimento A, Fernandes LA, Sgnotto FDR, Orfali RL, Aoki V, Duarte AJDS, Sanabani SS, Victor JR. IgG from Adult Atopic Dermatitis (AD) Patients Induces Thymic IL-22 Production and CLA Expression on CD4+ T Cells: Possible Epigenetic Implications Mediated by miRNA. Int J Mol Sci 2022; 23:6867. [PMID: 35743308 PMCID: PMC9224968 DOI: 10.3390/ijms23126867] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2022] [Revised: 06/10/2022] [Accepted: 06/11/2022] [Indexed: 11/30/2022] Open
Abstract
Atopic dermatitis (AD) is a common relapsing inflammatory skin disorder characterized by immune-mediated inflammation and epidermal barrier dysfunction. The pathogenesis of AD is multifactorial and has not been fully elucidated to date. This study aimed to evaluate whether serum IgG from adult AD patients could modulate the thymic maturation of IL-22-producing T cells and CLA+ T cells of non-atopic infants. Given that miRNAs regulate immune response genes, we evaluated whether miRNA expression is also altered in cultured thymocytes. Thymocytes were cultured with purified IgG from AD patients or control conditions (mock, Intravenous-IgG (IVIg), non-atopic IgG, or atopic non-AD IgG). Using flow cytometry analysis, we assessed the expression of CLA and intracellular levels of IL-4, IFN-γ, and IL-22 on double-positive T cells (DP T), CD4 T cells, or CD8 T cells. We also investigated the frequency of IgG isotypes and their direct interaction with the thymic T cells membrane. The miRNA profiles were evaluated by the Illumina small RNA-seq approach. MiRNA target gene prediction and enrichment analyses were performed using bioinformatics. Increased frequencies of IL-22 and CLA+ producing CD4+ T cells cultured with IgG of AD patients was seen in non-atopic infant thymocytes compared to all control conditions. No alterations were observed in the frequency of IgG isotypes among evaluated IgG pools. Evidence for a direct interaction between IgG and thymic DP T, CD4 T, and CD8 T cells is presented. The small RNA-seq analysis identified ten mature miRNAs that were modulated by AD IgG compared to mock condition (miR-181b-5p, hsa-miR-130b-3p, hsa-miR-26a-5p, hsa-miR-4497, has-miR-146a, hsa-let-7i-5p, hsa-miR-342-3p, has-miR-148a-3p, has-miR-92a and has-miR-4492). The prediction of the targetome of the seven dysregulated miRNAs between AD and mock control revealed 122 putative targets, and functional and pathway enrichment analyses were performed. Our results enhance our understanding of the mechanism by which IgG can collaborate in thymic T cells in the setting of infant AD.
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Affiliation(s)
- Thamires Rodrigues de Sousa
- Laboratory of Medical Investigation LIM-56, Division of Dermatology, Medical School, University of Sao Paulo, Av. Dr. Enéas Carvalho de Aguiar 500, Sao Paulo 05403-000, Brazil; (T.R.d.S.); (B.O.F.); (R.L.O.); (V.A.); (A.J.d.S.D.)
| | - Beatriz Oliveira Fagundes
- Laboratory of Medical Investigation LIM-56, Division of Dermatology, Medical School, University of Sao Paulo, Av. Dr. Enéas Carvalho de Aguiar 500, Sao Paulo 05403-000, Brazil; (T.R.d.S.); (B.O.F.); (R.L.O.); (V.A.); (A.J.d.S.D.)
| | - Andrezza Nascimento
- Post-Graduation Program in Translational Medicine, Federal University of São Paulo, Sao Paulo 04039-002, Brazil; (A.N.); (L.A.F.)
| | - Lorena Abreu Fernandes
- Post-Graduation Program in Translational Medicine, Federal University of São Paulo, Sao Paulo 04039-002, Brazil; (A.N.); (L.A.F.)
| | | | - Raquel Leão Orfali
- Laboratory of Medical Investigation LIM-56, Division of Dermatology, Medical School, University of Sao Paulo, Av. Dr. Enéas Carvalho de Aguiar 500, Sao Paulo 05403-000, Brazil; (T.R.d.S.); (B.O.F.); (R.L.O.); (V.A.); (A.J.d.S.D.)
| | - Valéria Aoki
- Laboratory of Medical Investigation LIM-56, Division of Dermatology, Medical School, University of Sao Paulo, Av. Dr. Enéas Carvalho de Aguiar 500, Sao Paulo 05403-000, Brazil; (T.R.d.S.); (B.O.F.); (R.L.O.); (V.A.); (A.J.d.S.D.)
| | - Alberto José da Silva Duarte
- Laboratory of Medical Investigation LIM-56, Division of Dermatology, Medical School, University of Sao Paulo, Av. Dr. Enéas Carvalho de Aguiar 500, Sao Paulo 05403-000, Brazil; (T.R.d.S.); (B.O.F.); (R.L.O.); (V.A.); (A.J.d.S.D.)
- Division of Pathology, Medical School, University of Sao Paulo, Sao Paulo 05403-000, Brazil
| | - Sabri Saeed Sanabani
- Laboratory of Medical Investigation LIM-56, Division of Dermatology, Medical School, University of Sao Paulo, Av. Dr. Enéas Carvalho de Aguiar 500, Sao Paulo 05403-000, Brazil; (T.R.d.S.); (B.O.F.); (R.L.O.); (V.A.); (A.J.d.S.D.)
- Laboratory of Medical Investigation LIM-03, Division of Pathology, Medical School, University of Sao Paulo, Sao Paulo 05403-000, Brazil
| | - Jefferson Russo Victor
- Laboratory of Medical Investigation LIM-56, Division of Dermatology, Medical School, University of Sao Paulo, Av. Dr. Enéas Carvalho de Aguiar 500, Sao Paulo 05403-000, Brazil; (T.R.d.S.); (B.O.F.); (R.L.O.); (V.A.); (A.J.d.S.D.)
- Faculdades Metropolitanas Unidas (FMU), Health Sciences School, Sao Paulo 04505-002, Brazil
- Medical School, Universidade Santo Amaro (UNISA), Sao Paulo 04829-300, Brazil
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14
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Mustafin RN. Molecular genetics of idiopathic pulmonary fibrosis. Vavilovskii Zhurnal Genet Selektsii 2022; 26:308-318. [PMID: 35795226 PMCID: PMC9170936 DOI: 10.18699/vjgb-22-37] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Revised: 09/14/2021] [Accepted: 01/13/2022] [Indexed: 11/19/2022] Open
Abstract
Idiopathic pulmonary fibrosis (IPF) is a severe progressive interstitial lung disease with a prevalence of 2 to 29 per 100,000 of the world’s population. Aging is a significant risk factor for IPF, and the mechanisms of aging (telomere depletion, genomic instability, mitochondrial dysfunction, loss of proteostasis) are involved in the pathogenesis of IPF. The pathogenesis of IPF consists of TGF-β activation, epithelial-mesenchymal transition, and SIRT7 expression decrease. Genetic studies have shown a role of mutations and polymorphisms in mucin genes (MUC5B), in the genes responsible for the integrity of telomeres (TERC, TERC, TINF2, DKC1, RTEL1, PARN), in surfactant-related genes (SFTPC, SFTPCA, SFTPA2, ABCA3, SP-A2), immune system genes (IL1RN, TOLLIP), and haplotypes of HLA genes (DRB1*15:01, DQB1*06:02) in IPF pathogenesis. The investigation of the influence of reversible epigenetic factors on the development of the disease, which can be corrected by targeted therapy, shows promise. Among them, an association of a number of specific microRNAs and long noncoding RNAs was revealed with IPF. Therefore, dysregulation of transposons, which serve as key sources of noncoding RNA and affect mechanisms of aging, may serve as a driver for IPF development. This is due to the fact that pathological activation of transposons leads to violation of the regulation of genes, in the epigenetic control of which microRNA originating from these transposons are involved (due to the complementarity of nucleotide sequences). Analysis of the MDTE database (miRNAs derived from Transposable Elements) allowed the detection of 12 different miRNAs derived in evolution
from transposons and associated with IPF (miR-31, miR-302, miR-326, miR-335, miR-340, miR-374, miR-487, miR-493,
miR-495, miR-630, miR-708, miR-1343). We described the relationship of transposons with TGF-β, sirtuins and
telomeres, dysfunction of which is involved in the pathogenesis of IPF. New data on IPF epigenetic mechanisms can
become the basis for improving results of targeted therapy of the disease using noncoding RNAs.
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15
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Naqvi RA, Datta M, Khan SH, Naqvi AR. Regulatory roles of MicroRNA in shaping T cell function, differentiation and polarization. Semin Cell Dev Biol 2022; 124:34-47. [PMID: 34446356 PMCID: PMC11661912 DOI: 10.1016/j.semcdb.2021.08.003] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Revised: 07/09/2021] [Accepted: 08/07/2021] [Indexed: 12/12/2022]
Abstract
T lymphocytes are an integral component of adaptive immunity with pleotropic effector functions. Impairment of T cell activity is implicated in various immune pathologies including autoimmune diseases, AIDS, carcinogenesis, and periodontitis. Evidently, T cell differentiation and function are under robust regulation by various endogenous factors that orchestrate underlying molecular pathways. MicroRNAs (miRNA) are a class of noncoding, regulatory RNAs that post-transcriptionally control multiple mRNA targets by sequence-specific interaction. In this article, we will review the recent progress in our understanding of miRNA-gene networks that are uniquely required by specific T cell effector functions and provide miRNA-mediated mechanisms that govern the fate of T cells. A subset of miRNAs may act in a synergistic or antagonistic manner to exert functional suppression of genes and regulate pathways that control T cell activation and differentiation. Significance of T cell-specific miRNAs and their dysregulation in immune-mediated diseases is discussed. Exosome-mediated horizontal transfer of miRNAs from antigen presenting cells (APCs) to T cells and from one T cell to another T cell subset and their impact on recipient cell functions is summarized.
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Affiliation(s)
- Raza Ali Naqvi
- Department of Periodontics, College of Dentistry, University of Illinois at Chicago, Chicago 60612, IL, USA.
| | - Manali Datta
- Amity Institute of Biotechnology, Amity University Rajasthan, Jaipur, Rajasthan, India
| | - Samia Haseeb Khan
- Graduate School of Medicine, Science and Technology, Shinshu University, 8304 Minami-Minowa, Kami-Ina, Nagano 399-4598, Japan
| | - Afsar R Naqvi
- Department of Periodontics, College of Dentistry, University of Illinois at Chicago, Chicago 60612, IL, USA.
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16
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Liang J, Liu XH, Chen XM, Song XL, Li W, Huang Y. Emerging Roles of Non-Coding RNAs in Childhood Asthma. Front Pharmacol 2022; 13:856104. [PMID: 35656293 PMCID: PMC9152219 DOI: 10.3389/fphar.2022.856104] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2022] [Accepted: 04/11/2022] [Indexed: 11/13/2022] Open
Abstract
Asthma is a chronic airway inflammatory disease in children characterized by airway inflammation, airway hyperresponsiveness and airway remodeling. Childhood asthma is usually associated with allergy and atopy, unlike adult asthma, which is commonly associated with obesity, smoking, etc. The pathogenesis and diagnosis of childhood asthma also remains more challenging than adult asthma, such as many diseases showing similar symptoms may coexist and be confused with asthma. In terms of the treatment, although most childhood asthma can potentially be self-managed and controlled with drugs, approximately 5-10% of children suffer from severe uncontrolled asthma, which carries significant health and socioeconomic burdens. Therefore, it is necessary to explore the pathogenesis of childhood asthma from a new perspective. Studies have revealed that non-coding RNAs (ncRNAs) are involved in the regulation of respiratory diseases. In addition, altered expression of ncRNAs in blood, and in condensate of sputum or exhalation affects the progression of asthma via regulating immune response. In this review, we outline the regulation and pathogenesis of asthma and summarize the role of ncRNAs in childhood asthma. We also hold promise that ncRNAs may be used for the development of biomarkers and support a new therapeutic strategy for childhood asthma.
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Affiliation(s)
- Juan Liang
- Department of Pediatrics, The Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.,Graduate School of Guangdong Medical University, Zhanjiang, China
| | - Xiao-Hua Liu
- Department of Pediatrics, The Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.,Graduate School of Guangdong Medical University, Zhanjiang, China
| | - Xue-Mei Chen
- Department of Pediatrics, The Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.,Graduate School of Guangdong Medical University, Zhanjiang, China
| | - Xiu-Ling Song
- Department of Pediatrics, The Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.,Graduate School of Guangdong Medical University, Zhanjiang, China
| | - Wen Li
- Department of Pediatrics, The Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
| | - Yuge Huang
- Department of Pediatrics, The Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
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17
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Lv JN, Li JQ, Cui YB, Ren YY, Fu YJ, Jiang YJ, Shang H, Zhang ZN. Plasma MicroRNA Signature Panel Predicts the Immune Response After Antiretroviral Therapy in HIV-Infected Patients. Front Immunol 2021; 12:753044. [PMID: 34887859 PMCID: PMC8650117 DOI: 10.3389/fimmu.2021.753044] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Accepted: 11/02/2021] [Indexed: 12/12/2022] Open
Abstract
Background Approximately 10–40% of people with human immunodeficiency virus (HIV) infection are unable to obtain successful improvements in immune function after antiretroviral therapy (ART). These patients are at greater risk of developing non-acquired immunodeficiency syndrome (AIDS)-related conditions, with the accompanying increased morbidity and mortality. Discovering predictive biomarkers can help to identify patients with a poor immune response earlier and provide new insights into the mechanisms of this condition. Methods A total of 307 people with HIV were enrolled, including 110 immune non-responders (INRs) and 197 immune responders (IRs). Plasma samples were taken before ART, and quantities of plasma microRNAs (miRNAs) were determined using reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR). Candidate biomarkers were established through four phases: discovery, training, validation, and blinded test. Binary logistic regression was used to analyze the combined predictive capacity of the identified miRNAs. The effect of one miRNA, miR-16-5p, on T cell function was assessed in vitro. Results Expression of five miRNAs (miR-580, miR-627, miR-138-5p, miR-16-5p, and miR-323-3p) was upregulated in the plasma of INRs compared with that in IRs. Expression of these miRNAs was negatively correlated with both CD4+ T cell counts and the increase in the proportion of CD4+ T cells after one year of ART. These five miRNAs were combined in a predictive model, which could effectively identify INRs or IRs. Furthermore, we found that miR-16-5p inhibits CD4+ T cell proliferation by regulating calcium flux. Conclusion We established a five-miRNA panel in plasma that accurately predicts poor immune response after ART, which could inform strategies to reduce the incidence of this phenomenon and improve the clinical management of these patients.
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Affiliation(s)
- Jun-Nan Lv
- National Health Commission (NHC) Key Laboratory of AIDS Immunology (China Medical University), National Clinical Research Center for Laboratory Medicine, The First Affiliated Hospital of China Medical University, Shenyang, China.,Key Laboratory of AIDS Immunology, Chinese Academy of Medical Sciences, Shenyang, China
| | - Jia-Qi Li
- National Health Commission (NHC) Key Laboratory of AIDS Immunology (China Medical University), National Clinical Research Center for Laboratory Medicine, The First Affiliated Hospital of China Medical University, Shenyang, China.,Key Laboratory of AIDS Immunology, Chinese Academy of Medical Sciences, Shenyang, China
| | - Ying-Bin Cui
- R&D Department, Beijing Quantobio Star Biotechnology Co., Ltd., Beijing, China
| | - Yuan-Yuan Ren
- National Health Commission (NHC) Key Laboratory of AIDS Immunology (China Medical University), National Clinical Research Center for Laboratory Medicine, The First Affiliated Hospital of China Medical University, Shenyang, China.,Key Laboratory of AIDS Immunology, Chinese Academy of Medical Sciences, Shenyang, China
| | - Ya-Jing Fu
- National Health Commission (NHC) Key Laboratory of AIDS Immunology (China Medical University), National Clinical Research Center for Laboratory Medicine, The First Affiliated Hospital of China Medical University, Shenyang, China.,Key Laboratory of AIDS Immunology, Chinese Academy of Medical Sciences, Shenyang, China
| | - Yong-Jun Jiang
- National Health Commission (NHC) Key Laboratory of AIDS Immunology (China Medical University), National Clinical Research Center for Laboratory Medicine, The First Affiliated Hospital of China Medical University, Shenyang, China.,Key Laboratory of AIDS Immunology, Chinese Academy of Medical Sciences, Shenyang, China
| | - Hong Shang
- National Health Commission (NHC) Key Laboratory of AIDS Immunology (China Medical University), National Clinical Research Center for Laboratory Medicine, The First Affiliated Hospital of China Medical University, Shenyang, China.,Key Laboratory of AIDS Immunology, Chinese Academy of Medical Sciences, Shenyang, China
| | - Zi-Ning Zhang
- National Health Commission (NHC) Key Laboratory of AIDS Immunology (China Medical University), National Clinical Research Center for Laboratory Medicine, The First Affiliated Hospital of China Medical University, Shenyang, China.,Key Laboratory of AIDS Immunology, Chinese Academy of Medical Sciences, Shenyang, China
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18
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Role of Epigenetics in the Pathogenesis, Treatment, Prediction, and Cellular Transformation of Asthma. Mediators Inflamm 2021; 2021:9412929. [PMID: 34566492 PMCID: PMC8457970 DOI: 10.1155/2021/9412929] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2021] [Accepted: 08/27/2021] [Indexed: 12/15/2022] Open
Abstract
Asthma is a mysterious disease with heterogeneity in etiology, pathogenesis, and clinical phenotypes. Although ongoing studies have provided a better understanding of asthma, its natural history, progression, pathogenesis, diversified phenotypes, and even the exact epigenetic linkage between childhood asthma and adult-onset/old age asthma remain elusive in many aspects. Asthma heritability has been established through genetic studies, but genetics is not the only influencing factor in asthma. The increasing incidence and some unsolved queries suggest that there may be other elements related to asthma heredity. Epigenetic mechanisms link genetic and environmental factors with developmental trajectories in asthma. This review provides an overview of asthma epigenetics and its components, including several epigenetic studies on asthma, and discusses the epigenetic linkage between childhood asthma and adult-onset/old age asthma. Studies involving asthma epigenetics present valuable novel approaches to solve issues related to asthma. Asthma epigenetic research guides us towards gene therapy and personalized T cell therapy, directs the discovery of new therapeutic agents, predicts long-term outcomes in severe cases, and is also involved in the cellular transformation of childhood asthma to adult-onset/old age asthma.
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19
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Tubita V, Callejas‐Díaz B, Roca‐Ferrer J, Marin C, Liu Z, Wang DY, Mullol J. Role of microRNAs in inflammatory upper airway diseases. Allergy 2021; 76:1967-1980. [PMID: 33314198 DOI: 10.1111/all.14706] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2020] [Revised: 11/25/2020] [Accepted: 12/04/2020] [Indexed: 12/12/2022]
Abstract
MicroRNAs (miRNAs) are a conserved family of small endogenous noncoding RNA molecules that modulate post-transcriptional gene expression in physiological and pathological processes. miRNAs can silence target mRNAs through degradation or inhibition of translation, showing their pivotal role in the pathogenesis of many human diseases. miRNAs play a role in regulating immune functions and inflammation and are implicated in controlling the development and activation of T and B cells. Inflammatory chronic upper airway diseases, such as rhinitis and rhinosinusitis, are spread all over the world and characterized by an exaggerated inflammation involving a complex interaction between immune and resident cells. Until now and despite allergy, little is known about their etiology and the processes implicated in the immune response and tuning inflammation of these diseases. This review highlights the knowledge of the current literature about miRNAs in inflammatory chronic upper airways diseases and how this may be exploited in the development of new clinical and therapeutic strategies.
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Affiliation(s)
- Valeria Tubita
- INGENIO Immunoal·lèrgia Respiratòria Clínica i Experimental (IRCE) Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) Universitat de Barcelona Barcelona Spain
| | - Borja Callejas‐Díaz
- INGENIO Immunoal·lèrgia Respiratòria Clínica i Experimental (IRCE) Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) Universitat de Barcelona Barcelona Spain
- CIBER of Respiratory Diseases (CIBERES) Carlos III Institute Barcelona Spain
| | - Jordi Roca‐Ferrer
- INGENIO Immunoal·lèrgia Respiratòria Clínica i Experimental (IRCE) Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) Universitat de Barcelona Barcelona Spain
- CIBER of Respiratory Diseases (CIBERES) Carlos III Institute Barcelona Spain
| | - Concepció Marin
- INGENIO Immunoal·lèrgia Respiratòria Clínica i Experimental (IRCE) Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) Universitat de Barcelona Barcelona Spain
- CIBER of Respiratory Diseases (CIBERES) Carlos III Institute Barcelona Spain
| | - Zheng Liu
- Department of Otolaryngology Head and Neck Surgery Tongji HospitalTongji Medical CollegeHuazhong University of Science and Technology Wuhan China
| | - De Yun Wang
- Department of Otolaryngology Yong Loo Lin School of MedicineNational University of SingaporeNational University Health System Singapore Singapore
| | - Joaquim Mullol
- INGENIO Immunoal·lèrgia Respiratòria Clínica i Experimental (IRCE) Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) Universitat de Barcelona Barcelona Spain
- CIBER of Respiratory Diseases (CIBERES) Carlos III Institute Barcelona Spain
- ENT Department Rhinology Unit & Smell Clinic Hospital Clínic de BarcelonaUniversitat de Barcelona Barcelona Spain
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20
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Fiuza BSD, Fonseca HF, Meirelles PM, Marques CR, da Silva TM, Figueiredo CA. Understanding Asthma and Allergies by the Lens of Biodiversity and Epigenetic Changes. Front Immunol 2021; 12:623737. [PMID: 33732246 PMCID: PMC7957070 DOI: 10.3389/fimmu.2021.623737] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2020] [Accepted: 02/08/2021] [Indexed: 12/12/2022] Open
Abstract
Exposure to different organisms (bacteria, mold, virus, protozoan, helminths, among others) can induce epigenetic changes affecting the modulation of immune responses and consequently increasing the susceptibility to inflammatory diseases. Epigenomic regulatory features are highly affected during embryonic development and are responsible for the expression or repression of different genes associated with cell development and targeting/conducting immune responses. The well-known, "window of opportunity" that includes maternal and post-natal environmental exposures, which include maternal infections, microbiota, diet, drugs, and pollutant exposures are of fundamental importance to immune modulation and these events are almost always accompanied by epigenetic changes. Recently, it has been shown that these alterations could be involved in both risk and protection of allergic diseases through mechanisms, such as DNA methylation and histone modifications, which can enhance Th2 responses and maintain memory Th2 cells or decrease Treg cells differentiation. In addition, epigenetic changes may differ according to the microbial agent involved and may even influence different asthma or allergy phenotypes. In this review, we discuss how exposure to different organisms, including bacteria, viruses, and helminths can lead to epigenetic modulations and how this correlates with allergic diseases considering different genetic backgrounds of several ancestral populations.
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Affiliation(s)
| | | | - Pedro Milet Meirelles
- Instituto de Biologia, Universidade Federal da Bahia, Salvador, Brazil
- Instituto Nacional de Ciência e Tecnologia em Estudos Interdisciplinares e Transdisciplinares em Ecologia e Evolução (IN-TREE), Salvador, Brazil
| | - Cintia Rodrigues Marques
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista, Brazil
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21
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Bu X, Wang M, Luan G, Wang Y, Wang C, Zhang L. Integrated miRNA and mRNA expression profiling reveals dysregulated miRNA-mRNA regulatory networks in eosinophilic and non-eosinophilic chronic rhinosinusitis with nasal polyps. Int Forum Allergy Rhinol 2021; 11:1207-1219. [PMID: 33611865 DOI: 10.1002/alr.22781] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2020] [Revised: 01/06/2021] [Accepted: 01/24/2021] [Indexed: 01/02/2023]
Abstract
BACKGROUND The precise mechanisms underlying pathogenesis of different subtypes of chronic rhinosinusitis with nasal polyps (CRSwNP) are still unclear. Emerging evidence indicates that microRNAs may play a role in the pathogenesis of CRSwNP. This study aimed to identify the dysregulated microRNA-messenger RNA (miRNA-mRNA) regulatory networks in eosinophilic (E) and non-eosinophilic (non-E) CRSwNP. METHODS Whole-transcriptome sequencing was performed on nasal tissues of patients with ECRSwNP and non-ECRSwNP, and control subjects. An integrated analysis of miRNA and mRNA expression was conducted to identify key mRNAs and miRNAs involved in the pathogenesis of ECRSwNP and non-ECRSwNP. The miRNAs of interest and their target genes were validated using quantitative real-time polymerase chain reaction (PCR). RESULTS A group of differentially expressed mRNAs (DE-mRNAs) and miRNAs (DE-miRs) were identified in ECRSwNP patients vs control subjects, non-ECRSwNP patients vs control subjects, and non-ECRSwNP vs ECRSwNP patients, respectively. Pathway enrichment analysis showed distinct immune and inflammatory functions associated with DE-mRNAs and target genes of DE-miRs in ECRSwNP vs control and non-ECRSwNP vs control groups. The miRNA-mRNA regulatory networks constructed with Cytoscape highlighted the roles of miR-154, miR-221, and miR-223 family miRNAs relating to both ECRSwNP and non-ECRSwNP, and the roles of the let-7 and miR-34/449 families in the development of non-ECRSwNP. Assessment using real-time PCR for the expression of miRNAs and target genes demonstrated highly consistent data with the RNA sequencing data. CONCLUSION ECRSwNP and non-ECRSwNP patients express distinct miRNA-mRNA regulatory networks compared with control subjects, thus providing potential targets for future development of novel therapeutic approaches for the management of CRSwNP.
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Affiliation(s)
- Xiangting Bu
- Department of Otolaryngology, Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, PR China.,Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, PR China
| | - Ming Wang
- Department of Otolaryngology, Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, PR China.,Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, PR China
| | - Ge Luan
- Department of Otolaryngology, Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, PR China.,Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, PR China
| | - Yang Wang
- Department of Otolaryngology, Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, PR China.,Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, PR China
| | - Chengshuo Wang
- Department of Otolaryngology, Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, PR China.,Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, PR China
| | - Luo Zhang
- Department of Otolaryngology, Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, PR China.,Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, PR China.,Department of Allergy, Beijing TongRen Hospital, Capital Medical University, Beijing, PR China
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22
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Abstract
PURPOSE OF REVIEW MicroRNAs (miRNAs) are small noncoding RNA molecules that are considered one of the fundamental regulatory mechanisms of gene expression. They are involved in many biologic processes, such as signal transduction, cell proliferation and differentiation, apoptosis and stress responses. The purpose of this review is to present recent knowledge about the role of miRNAs in asthma and outline possible applications of miRNAs. RECENT FINDINGS A core set of miRNAs involved in asthma includes downregulated let-7 family, miR-193b, miR-375 as well as upregulated miR-21, miR-223, miR-146a, miR-142-5p, miR-142-3p, miR-146b and miR-155. Recently it has been shown that most of the involved miRNAs increase secretion of Th2 cytokines, decrease secretion of Th1 cytokines, promote differentiation of T cells towards Th2 or play a role in hyperplasia and hypertrophy of bronchial smooth muscle cells. The profiles of miRNAs correlate with clinical characteristics, including lung function, phenotype and severity of asthma. SUMMARY Recent publications confirmed crucial regulatory role of miRNAs in the pathomechanism of asthma. Some single miRNAs or their sets hold the promise for their use as asthma biomarkers facilitating diagnosis or prediction of treatment outcomes. They are also possible target of future therapies. The studies in this field are lacking though.
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23
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Xu L, Yi M, Tan Y, Yi Z, Zhang Y. A comprehensive analysis of microRNAs as diagnostic biomarkers for asthma. Ther Adv Respir Dis 2020; 14:1753466620981863. [PMID: 33357010 PMCID: PMC7768876 DOI: 10.1177/1753466620981863] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Background: It is unclear whether microRNAs could be a potential diagnostic biomarker for asthma or not. The objective of this study is to figure out the diagnostic value of microRNAs in asthma. Methods: Literature retrieval, screening of publications, specific data extraction, and quality evaluation were conducted according to the standard criteria. Stata 14.0 software was used to analyze the diagnostic value of microRNA for asthma, including the combined sensitivity (Sen), specificity (Spe), the area under the curve (AUC), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR). Results: A total of 72 studies, containing 4143 cases and 2188 controls, were included for this comprehensive analysis. None of the included publications were rated low in quality. We summarized that, compared with controls, more than 100 miRNAs were reported differently expressed in asthma, although the expression trends were inconsistent. Besides, there were five studies among these 72 articles that applied the diagnostic evaluation of microRNAs in asthma. We found that the pooled Sen, Spe, and AUC for the combination of miR-185-5p, miR-155, let-7a, miR-21, miR-320a, miR-1246, miR-144-5p, and miR-1165-3p in asthma were 0.87 (95%CI: 0.72–0.95), 0.84 (95%CI: 0.74–0.91), and 0.93 (95%CI: 0.89–0.94) individually, and the PLR, NLR, and DOR were 5.5 (95%CI: 3.1–9.7), 0.15 (95%CI: 0.07–0.36), and 35 (95%CI: 10–127) in asthma, respectively. In terms of subgroup analyses, we found that the Sen for these combination miRNAs from serum was higher than that in plasma, while the Spe in plasma worked better than that in serum. Furthermore, compared with children, the combination of above miRNAs from adults had higher Spe and similar Sen. Conclusions: From our analysis, the combination of miR-185-5p, miR-155, let-7a, miR-21, miR-320a, miR-1246, miR-144-5p, and miR-1165-3p from peripheral blood could potentially act as a diagnostic biomarker for asthma. The reviews of this paper are available via the supplemental material section.
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Affiliation(s)
- Li Xu
- Department of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China.,School of Life Sciences, Central South University, Changsha, Hunan, China.,National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Minhan Yi
- School of Life Sciences, Central South University, Changsha, Hunan, China
| | - Yun Tan
- School of Life Sciences, Central South University, Changsha, Hunan, China
| | - Zixun Yi
- School of Life Sciences, Central South University, Changsha, Hunan, China
| | - Yuan Zhang
- Department of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.,National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
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24
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Mu Z, Zhang J. The Role of Genetics, the Environment, and Epigenetics in Atopic Dermatitis. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2020; 1253:107-140. [PMID: 32445093 DOI: 10.1007/978-981-15-3449-2_4] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Atopic Dermatitis (AD) is a common inflammatory disease with a genetic background. The prevalence of AD has been increasing in many countries. AD patients often have manifestations of pruritus, generalized skin dryness, and eczematous lesions. The pathogenesis of AD is complicated. The impaired skin barrier and immune imbalance play significant roles in the development of AD. Environmental factors such as allergens and pollutants are associated with the increasing prevalence. Many genetic and environmental factors induce a skin barrier deficiency, and this can lead to immune imbalance, which exacerbates the impaired skin barrier to form a vicious cycle (outside-inside-outside view). Genetic studies find many gene mutations and genetic variants, such as filaggrin mutations, which may directly induce the deficiency of the skin barrier and immune system. Epigenetic studies provide a connection between the relationship of an impaired skin barrier and immune and environmental factors, such as tobacco exposure, pollutants, microbes, and diet and nutrients. AD is a multigene disease, and thus there are many targets for regulation of expression of these genes which may contribute to the pathogenesis of AD. However, the epigenetic regulation of environmental factors in AD pathogenesis still needs to be further researched.
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Affiliation(s)
- Zhanglei Mu
- Department of Dermatology, Peking University People's Hospital, Beijing, China
| | - Jianzhong Zhang
- Department of Dermatology, Peking University People's Hospital, Beijing, China.
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25
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Sugita K, Akdis CA. Recent developments and advances in atopic dermatitis and food allergy. Allergol Int 2020; 69:204-214. [PMID: 31648922 DOI: 10.1016/j.alit.2019.08.013] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2019] [Revised: 08/26/2019] [Accepted: 08/28/2019] [Indexed: 02/07/2023] Open
Abstract
This review highlights recent advances in atopic dermatitis (AD) and food allergy (FA), particularly on molecular mechanisms and disease endotypes, recent developments in global strategies for the management of patients, pipeline for future treatments, primary and secondary prevention and psychosocial aspects. During the recent years, there has been major advances in personalized/precision medicine linked to better understanding of disease pathophysiology and precision treatment options of AD. A greater understanding of the molecular and cellular mechanisms of AD through substantial progress in epidemiology, genetics, skin immunology and psychological aspects resulted in advancements in the precision management of AD. However, the implementation of precision medicine in the management of AD still requires the validation of reliable biomarkers, which will provide more tailored management, starting from prevention strategies towards targeted therapies for more severe diseases. Cutaneous exposure to food via defective barriers is an important route of sensitization to food allergens. Studies on the role of the skin barrier genes demonstrated their association with the development of IgE-mediated FA, and suggest novel prevention and treatment strategies for type 2 diseases in general because of their link to barrier defects not only in AD and FA, but also in asthma, chronic rhinosinusitis, allergic rhinitis and inflammatory bowel disease. The development of more accurate diagnostic tools, biomarkers for early prediction, and innovative solutions require a better understanding of molecular mechanisms and the pathophysiology of FA. Based on these developments, this review provides an overview of novel developments and advances in AD and FA, which are reported particularly during the last two years.
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26
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Fan JM, Zheng ZR, Zeng YM, Chen XY. MiR-323-3p Targeting Transmembrane Protein with EGF-Like and 2 Follistatin Domain (TMEFF2) Inhibits Human Lung Cancer A549 Cell Apoptosis by Regulation of AKT and ERK Signaling Pathways. Med Sci Monit 2020; 26:e919454. [PMID: 32009129 PMCID: PMC7011573 DOI: 10.12659/msm.919454] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Background Non-small-cell lung cancer (NSCLC) is predominant and has low 5-year relative survival rate. Therefore, the mechanisms of NSCLC tumorigenesis must be comprehensively elucidated. MicroRNA-323-3p (miR-323-3p) has been widely explored and found to exert functions in tumorigenesis of several cancer types. However, the expression pattern and biological function of miR-323-3p and the molecular mechanism underlying NSCLC development and progression remain unclear. Material/Methods Quantitative reverse-transcription polymerase chain reaction was used to detect the expression of miR-323-3p and TMEFF2 in NSCLC cell lines (A549, NCI-H3255, and H1299) and normal cell line (BEAS-2B). Methylthiazolyl tetrazolium, colony formation, and flow cytometry assays were performed to evaluate the effects of miR-323-3p and TMEFF2 on cell proliferation. Transwell assay was conducted to determine the effects of TMEFF2 on cell migration and invasion. Dual-luciferase reporter assay was used to verify whether TMEFF2 is a target of miR-323-3p. Western blot analysis was performed to analyze protein expression. Results The expression of miR-323-3p increased in the 3 NSCLC cell lines (A549, NCI-H3255, and H1299). miR-323-3p regulated cellular progression by directly suppressing TMEFF2 expression and indirectly prohibited the activation of AKT and ERK pathways in NSCLC. Conclusions Overall, miR-323-3p was considered a lung cancer oncogene and could be a valuable target for NSCLC therapy.
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Affiliation(s)
- Ji-Min Fan
- Department of Pulmonary and Critical Care Medicine, Second Affiliated Hospital of Fujian Medical University, Respiratory Medicine Center of Fujian Province, Quanzhou, Fujian, China (mainland)
| | - Zheng-Rong Zheng
- Department of Surgical Oncology, Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China (mainland)
| | - Yi-Ming Zeng
- Department of Pulmonary and Critical Care Medicine, Second Affiliated Hospital of Fujian Medical University, Respiratory Medicine Center of Fujian Province, Quanzhou, Fujian, China (mainland)
| | - Xiao-Yang Chen
- Department of Pulmonary and Critical Care Medicine, Second Affiliated Hospital of Fujian Medical University, Respiratory Medicine Center of Fujian Province, Quanzhou, Fujian, China (mainland)
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27
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Taka S, Tzani-Tzanopoulou P, Wanstall H, Papadopoulos NG. MicroRNAs in Asthma and Respiratory Infections: Identifying Common Pathways. ALLERGY, ASTHMA & IMMUNOLOGY RESEARCH 2020; 12:4-23. [PMID: 31743961 PMCID: PMC6875476 DOI: 10.4168/aair.2020.12.1.4] [Citation(s) in RCA: 46] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/12/2019] [Revised: 07/15/2019] [Accepted: 07/16/2019] [Indexed: 12/27/2022]
Abstract
MicroRNAs (miRs) are single-stranded RNAs of 18-25 nucleotides. These molecules regulate gene expression at the post-transcriptional level; several of these are differentially expressed in asthma as well as in viral acute respiratory infections (ARIs), the main triggers of acute asthma exacerbations. In recent years, miRs have been studied in order to discover drug targets as well as biomarkers for diagnosis, disease severity and prognosis. We describe recent findings on miR expression and function in asthma and their role in the regulation of viral ARIs, according to cell tissue specificity and asthma severity. By combining the above information, we identify miRs that may be important in virus-induced asthma exacerbations. This is the first attempt to link miR profiles of asthmatic patients and ARI-induced miRs, addressing the question of whether there might be a specific miR deficit in asthmatic subjects that make them more susceptible and/or reactive to infection.
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Affiliation(s)
- Styliani Taka
- Allergy and Clinical Immunology Unit, 2nd Pediatric Clinic, National and Kapodistrian University of Athens, Athens, Greece
| | - Panayiota Tzani-Tzanopoulou
- Allergy and Clinical Immunology Unit, 2nd Pediatric Clinic, National and Kapodistrian University of Athens, Athens, Greece
| | - Hannah Wanstall
- Allergy and Clinical Immunology Unit, 2nd Pediatric Clinic, National and Kapodistrian University of Athens, Athens, Greece.,Division of Infection, Inflammation and Respiratory Medicine, University of Manchester, Manchester, United Kingdom
| | - Nikolaos G Papadopoulos
- Allergy and Clinical Immunology Unit, 2nd Pediatric Clinic, National and Kapodistrian University of Athens, Athens, Greece.,Division of Infection, Inflammation and Respiratory Medicine, University of Manchester, Manchester, United Kingdom.
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28
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Meng Y, Wang C, Zhang L. Recent developments and highlights in allergic rhinitis. Allergy 2019; 74:2320-2328. [PMID: 31571226 DOI: 10.1111/all.14067] [Citation(s) in RCA: 107] [Impact Index Per Article: 17.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2019] [Revised: 09/24/2019] [Accepted: 09/26/2019] [Indexed: 12/16/2022]
Abstract
Allergic rhinitis (AR) is a disease with high prevalence all over the world and therefore needs to be thoroughly investigated and treated accordingly. The mechanisms underlying the pathology and treatment of AR have been widely studied, but many aspects remain unclear and warrant further investigations. This review presents an overview of recently published papers highlighting the risk factors, mechanisms, and treatment of AR. Additionally, recent studies discussing the role of single nucleotide polymorphism, DNA methylation, regulatory B cells, group 2 innate lymphoid cells, immunotherapy, and biologics in AR are also covered.
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Affiliation(s)
- Yifan Meng
- Department of Otolaryngology Head and Neck Surgery Beijing TongRen Hospital Capital Medical University Beijing China
| | - Chengshuo Wang
- Department of Otolaryngology Head and Neck Surgery Beijing TongRen Hospital Capital Medical University Beijing China
| | - Luo Zhang
- Department of Otolaryngology Head and Neck Surgery Beijing TongRen Hospital Capital Medical University Beijing China
- Beijing Key Laboratory of Nasal Diseases Beijing Institute of Otolaryngology Beijing China
- Department of Allergy Beijing TongRen Hospital Capital Medical University Beijing China
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29
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Qi C, Xu CJ, Koppelman GH. The role of epigenetics in the development of childhood asthma. Expert Rev Clin Immunol 2019; 15:1287-1302. [PMID: 31674254 DOI: 10.1080/1744666x.2020.1686977] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Introduction: The development of childhood asthma is caused by a combination of genetic factors and environmental exposures. Epigenetics describes mechanisms of (heritable) regulation of gene expression that occur without changes in DNA sequence. Epigenetics is strongly related to aging, is cell-type specific, and includes DNA methylation, noncoding RNAs, and histone modifications.Areas covered: This review summarizes recent epigenetic studies of childhood asthma in humans, which mostly involve studies of DNA methylation published in the recent five years. Environmental exposures, in particular cigarette smoking, have significant impact on epigenetic changes, but few of these epigenetic signals are also associated with asthma. Several asthma-associated genetic variants relate to DNA methylation. Epigenetic signals can be better understood by studying their correlation with gene expression, which revealed higher presence and activation of blood eosinophils in asthma. Strong associations of nasal methylation signatures and atopic asthma were identified, which were replicable across different populations.Expert commentary: Epigenetic markers have been strongly associated with asthma, and might serve as biomarker of asthma. The causal and longitudinal relationships between epigenetics and disease, and between environmental exposures and epigenetic changes need to be further investigated. Efforts should be made to understand cell-type-specific epigenetic mechanisms in asthma.
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Affiliation(s)
- Cancan Qi
- Dept. of Pediatric Pulmonology and Pediatric Allergology, Beatrix Children's Hospital, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.,GRIAC Research Institute, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Cheng-Jian Xu
- Dept. of Pediatric Pulmonology and Pediatric Allergology, Beatrix Children's Hospital, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.,GRIAC Research Institute, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.,Department of Gastroenterology, Hepatology and Endocrinology, CiiM, Centre for individualised infection medicine, A joint venture between Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Germany.,TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Germany
| | - Gerard H Koppelman
- Dept. of Pediatric Pulmonology and Pediatric Allergology, Beatrix Children's Hospital, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.,GRIAC Research Institute, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
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30
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Huang R, Chen X, Long Y, Chen R. MiR-31 promotes Th22 differentiation through targeting Bach2 in coronary heart disease. Biosci Rep 2019; 39:BSR20190986. [PMID: 31501353 PMCID: PMC6753318 DOI: 10.1042/bsr20190986] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2019] [Revised: 08/28/2019] [Accepted: 09/06/2019] [Indexed: 12/11/2022] Open
Abstract
The aim of the present study was to investigate the role of miR-31 in Th22 differentiation in coronary heart disease (CHD). Th22 frequencies in peripheral blood of CHD patients and controls as well as in CD4+ T cells were detected by flow cytometry. The mRNA expression of Th22-associated transcription factor aryl hydrocarbon receptor (AHR) and Th22-effector cytokine interleukin (IL)-22, as well as miR-31 were examined by quantitative real-time PCR (qRT-PCR). The protein level of BTB domain and CNC homolog 2 (Bach2) was measured by Western blotting. The interaction between miR-31 and Bach2 was verified using dual luciferase reporter assay. The results showed that Th22 frequency and miR-31 expression were elevated in CHD patients. Furthermore, miR-31 mimic and Bach2 silencing significantly promoted Th22 frequency and the levels of AHR and IL-22 in CD4+ T cells from CHD patients. Further studies showed that miR-31 facilitated Th22 cell differentiation by targeting and inhibiting Bach2. Our data indicate that miR-31 promotes Th22 differentiation through targeting Bach2 in CHD.
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Affiliation(s)
- Rimao Huang
- Department of Cardiovascular Surgery, Xiangya Hospital of Centre-south University, No.87 Xiangya Road, Kaifu District, Changsha 410008, Hunan, China
| | - Xuliang Chen
- Department of Cardiovascular Surgery, Xiangya Hospital of Centre-south University, No.87 Xiangya Road, Kaifu District, Changsha 410008, Hunan, China
| | - Yadong Long
- Department of Cardiovascular Surgery, Xiangya Hospital of Centre-south University, No.87 Xiangya Road, Kaifu District, Changsha 410008, Hunan, China
| | - Ri Chen
- Department of Cardiovascular Surgery, Xiangya Hospital of Centre-south University, No.87 Xiangya Road, Kaifu District, Changsha 410008, Hunan, China
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31
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Specjalski K, Jassem E. MicroRNAs: Potential Biomarkers and Targets of Therapy in Allergic Diseases? Arch Immunol Ther Exp (Warsz) 2019; 67:213-223. [PMID: 31139837 PMCID: PMC6597590 DOI: 10.1007/s00005-019-00547-4] [Citation(s) in RCA: 108] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2019] [Accepted: 05/13/2019] [Indexed: 12/17/2022]
Abstract
MicroRNAs (miRNAs) are small non-coding RNA molecules that are 18-22 nucleotides long and highly conserved throughout evolution. Currently, they are considered one of the fundamental regulatory mechanisms of genes expression. It has been demonstrated that miRNAs are involved in many biologic processes, such as signal transduction, cell proliferation and differentiation, apoptosis and stress responses. More recently, the role of miRNA has also been revealed in numerous immunological and inflammatory disorders, including allergic inflammation. Specific miRNA profiles were demonstrated in asthma, allergic rhinitis and atopic dermatitis. A core set of miRNAs involved in atopic diseases include upregulated miR-21, miR-223, miR-146a, miR-142-5p, miR-142-3p, miR-146b, miR-155 and downregulated let-7 family, miR-193b and miR-375. Most of the involved miRNAs increase secretion of Th2 cytokines (miR-1248, miR-146b), decrease secretion of Th1 cytokines (miR-513-5p, miR-625-5p) or promote differentiation of T cells towards Th2 (miR-21, miR-19a). In asthma miR-140-3p, miR-708 and miR-142-3p play a role in hyperplasia and hypertrophy of bronchial smooth muscle cells. Some single miRNAs or, more probably, their sets hold the promise for their use as biomarkers of atopic diseases. They are also promising target of future therapies.
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Affiliation(s)
- Krzysztof Specjalski
- Department of Allergology, Medical University of Gdańsk, Dębinki 7, 80-210, Gdańsk, Poland.
| | - Ewa Jassem
- Department of Allergology, Medical University of Gdańsk, Dębinki 7, 80-210, Gdańsk, Poland
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32
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Mousavi SR, Ahmadi A, Jamalkandi SA, Salimian J. Involvement of microRNAs in physiological and pathological processes in asthma. J Cell Physiol 2019; 234:21547-21559. [PMID: 31099080 DOI: 10.1002/jcp.28781] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2018] [Revised: 04/19/2019] [Accepted: 04/22/2019] [Indexed: 12/31/2022]
Abstract
Asthma is the most common respiratory disease accompanied by lung inflammatory disorders. The main symptoms are airway obstruction, chronic inflammation due to mast cell and eosinophil activity, and the disturbance of immune responses mostly mediated by the Th2 response. Genetic background and environmental factors also contribute to the pathogenesis of asthma. Today, microRNAs (miRNAs) are known as remarkable regulators of gene expression. As a small group of noncoding single-strand RNAs, mature miRNAs (~21 nucleotides) modulate the gene expression by targeting complement RNAs at both transcriptional and posttranscriptional levels. The role of miRNAs in the pathogenesis of many diseases such as allergies, asthma, and autoimmunity has been vastly studied. This review provides a thorough research update on the role of miRNAs in the pathogenesis of asthma and their probable role as diagnostic and/or therapeutic biomarkers.
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Affiliation(s)
- Seyed Reza Mousavi
- Chemical Injuries Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Ali Ahmadi
- Molecular Biology Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Sadegh Azimzadeh Jamalkandi
- Chemical Injuries Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Jafar Salimian
- Chemical Injuries Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
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33
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Aldapa-Vega G, Moreno-Eutimio MA, Berlanga-Taylor AJ, Jiménez-Uribe AP, Nieto-Velazquez G, López-Ortega O, Mancilla-Herrera I, Cortés-Malagón EM, Gunn JS, Isibasi A, Wong-Baeza I, López-Macías C, Pastelin-Palacios R. Structural variants of Salmonella Typhimurium lipopolysaccharide induce less dimerization of TLR4/MD-2 and reduced pro-inflammatory cytokine production in human monocytes. Mol Immunol 2019; 111:43-52. [PMID: 30959420 DOI: 10.1016/j.molimm.2019.03.003] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2018] [Revised: 02/23/2019] [Accepted: 03/07/2019] [Indexed: 01/22/2023]
Abstract
Salmonella enterica serovar Typhimurium (S. Typhimurium) changes the structure of its lipopolysaccharide (LPS) in response to the environment. The two main LPS variants found in S. Typhimurium correspond to LPS with a hepta-acylated lipid A (LPS 430) and LPS with modified phosphate groups on its lipid A (LPS 435). We have previously shown that these modified LPS have a lower capacity than wild type (WT) LPS to induce the production of pro-inflammatory cytokines in mice. Nevertheless, it is not know if LPS 430 and LPS 435 could also subvert the innate immune responses in human cells. In this study, we found that LPS 430 and LPS 435 were less efficient than WT LPS to induce the production of pro-inflammatory cytokines by human monocytes, in addition we found a decreased dimerization of the TLR4/MD-2 complex in response to LPS 430, suggesting that structurally modified LPS are sensed differently than WT LPS by this receptor; however, LPS 430 and 435 induced similar activation of the transcription factors NF-κB p65, IRF3, p38 and ERK1/2 than WT LPS. Microarray analysis of LPS 430- and LPS 435-activated monocytes revealed a gene transcription profile with differences only in the expression levels of microRNA genes compared to the profile induced by WT LPS, suggesting that the lipid A modifications present in LPS 430 and LPS 435 have a moderate effect on the activation of the human TLR4/MD-2 complex. Our results are relevant to understand LPS modulation of immune responses and this knowledge could be useful for the development of novel adjuvants and immunomodulators.
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Affiliation(s)
- Gustavo Aldapa-Vega
- Unidad de Investigación Médica en Inmunoquímica, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de México, Mexico; Programa de Posgrado en Inmunología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Ciudad de México, Mexico
| | - Mario Adán Moreno-Eutimio
- Unidad de Investigación de Inmunidad e Inflamación, División de Investigación, Hospital Juárez de México, Ciudad de México, Mexico
| | - Antonio J Berlanga-Taylor
- MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Faculty of Medicine, Imperial College London, St Mary's Campus, Norfolk Place, London, UK
| | - Alexis P Jiménez-Uribe
- Unidad de Investigación Médica en Inmunoquímica, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de México, Mexico
| | - Goreti Nieto-Velazquez
- Unidad de Investigación de Inmunidad e Inflamación, División de Investigación, Hospital Juárez de México, Ciudad de México, Mexico
| | - Orestes López-Ortega
- Departamento de Biomedicina Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Ciudad de México, Mexico
| | - Ismael Mancilla-Herrera
- Departamento de Infectología e Inmunología, Instituto Nacional de Perinatología, Ciudad de México, Mexico
| | - Enoc Mariano Cortés-Malagón
- Unidad de Investigación en Genética y Cáncer, División de Investigación, Hospital Juárez de México, Ciudad de México, Mexico
| | - John S Gunn
- Department of Microbial Infection and Immunity, Infectious Diseases Institute, The Ohio State University, Columbus, OH, United States
| | - Armando Isibasi
- Unidad de Investigación Médica en Inmunoquímica, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de México, Mexico
| | - Isabel Wong-Baeza
- Laboratorio de Inmunología Molecular II, Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Ciudad de México, Mexico
| | - Constantino López-Macías
- Unidad de Investigación Médica en Inmunoquímica, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de México, Mexico; Visiting Professor of Immunology. Nuffield Department of Medicine, University of Oxford. UK; Mexican Translational Immunology Research Group, FOCIS Centres of Excellence, Mexico.
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34
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Agache I, Akdis CA. Precision medicine and phenotypes, endotypes, genotypes, regiotypes, and theratypes of allergic diseases. J Clin Invest 2019; 129:1493-1503. [PMID: 30855278 PMCID: PMC6436902 DOI: 10.1172/jci124611] [Citation(s) in RCA: 199] [Impact Index Per Article: 33.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
A rapidly developing paradigm for modern health care is a proactive and individualized response to patients' symptoms, combining precision diagnosis and personalized treatment. Precision medicine is becoming an overarching medical discipline that will require a better understanding of biomarkers, phenotypes, endotypes, genotypes, regiotypes, and theratypes of diseases. The 100-year-old personalized allergen-specific management of allergic diseases has particularly contributed to early awareness in precision medicine. Polyomics, big data, and systems biology have demonstrated a profound complexity and dynamic variability in allergic disease between individuals, as well as between regions. Escalating health care costs together with questionable efficacy of the current management of allergic diseases facilitated the emergence of the endotype-driven approach. We describe here a precision medicine approach that stratifies patients based on disease mechanisms to optimize management of allergic diseases.
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Affiliation(s)
- Ioana Agache
- Transylvania University, Faculty of Medicine, Brasov, Romania
| | - Cezmi A. Akdis
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
- Christine Kühne – Center for Allergy Research and Education (CK-CARE), Davos, Switzerland
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35
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Zhang Y, Wang L, Zhou X, Geng J, Li X. The immunomodulatory mechanism of brain injury induced by hyperhomocysteinemia in spontaneously hypertensive rats. J Cell Biochem 2019; 120:9421-9429. [PMID: 30681198 DOI: 10.1002/jcb.28217] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2018] [Accepted: 11/15/2018] [Indexed: 01/01/2023]
Abstract
BACKGROUND Elevated plasma homocysteine (Hcy) concentration is considered as the diagnostic criteria of Hyperhomocysteinemia (HHcy), which is associated with the inflammatory response and blood-brain barrier disruption. Previous studies have proposed that HHcy with hypertension was associated with the brain injury by enhancing the cerebrovascular permeability, however, the immune mechanism remains obscure. The purpose of the study is to explore the immunomodulatory mechanism of brain injury in spontaneously hypertensive rats (SHRs) induced by HHcy. MATERIALS AND METHODS Sixty SHRs were randomly assigned to three groups: SHR-C (control group), SHR-M (methionine group) and SHR-T (treatment group). Physical examination of body weight, systolic blood pressure (SBP) and plasma Hcy content was measured every 4 weeks. Besides, T-helper cell 17 and regulatory T cells (Treg)-related inflammatory cytokines (interleukin [IL]-6, IL-17, IL-10, and transforming growth factor beta [TGF-β]) and genes (RORγt and FoxP3) were detected by enzyme-linked immunosorbent assay, quantitative polymerase chain reaction , Western blot, and immunohistochemistry. RESULTS High methionine diet could cause weight loss, SBP rising, and plasma Hcy content significantly elevated. IL-16 and IL-17A levels in peripheral blood and in brain tissue both lifted, while IL-10 and TGF-β levels dropped; RORγt expression raised in brain, nevertheless, FoxP3 levels were the opposite. After the intervention with vitamin B6, B12, and folic acid in SHR-T group, these trends would be eased or completely changed. Furthermore, brain tissue slices showed that IL-17-positive cells tended to decrease, and IL-10-positive cells increased in SHR-T group, which was reversed in SHR-M group. CONCLUSIONS HHcy may promote inflammation that can lead to brain lesions and down-regulate immune response to protect the brain.
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Affiliation(s)
- Yu Zhang
- Department of Geriatric, the Second Hospital of Tianjin Medical University, Tianjin, China
| | - Lin Wang
- Department of Geriatric, the Second Hospital of Tianjin Medical University, Tianjin, China
| | - Xin Zhou
- Department of Cardiovascular disease and heart center, Pingjin Hospital, Logistics university of the Chinese people's armed police forces, Tianjin, China
| | - Jie Geng
- Department of Cardiology, Tianjin Chest Hospital, Tianjin, China
| | - Xin Li
- Department of Geriatric, the Second Hospital of Tianjin Medical University, Tianjin, China
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Ito T, Hirose K, Nakajima H. Bidirectional roles of IL-22 in the pathogenesis of allergic airway inflammation. Allergol Int 2019; 68:4-8. [PMID: 30424940 DOI: 10.1016/j.alit.2018.10.002] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2018] [Revised: 09/27/2018] [Accepted: 10/08/2018] [Indexed: 02/07/2023] Open
Abstract
Asthma is the most prevalent allergic disease of the airway, which is characterized by eosinophilic inflammation, mucus hyperproduction, and airway hyper-responsiveness. Although these pathognomonic features are mainly mediated by antigen-specific Th2 cells and their cytokines, such as IL-4, IL-5, and IL-13, recent studies have revealed that other inflammatory cells, including Th17 cells and innate lymphoid cells (ILCs), also play a critical role in the pathogenesis of asthma. IL-22, one of the cytokines produced by Th17 cells and type 3 ILCs, has distinct functional properties, as IL-22 exclusively acts on non-hematopoietic cells including epithelial cells of mucosal surface and exhibits a broad range of action in regeneration and host protection. In accordance with the fact that lung epithelial cells play a critical role in the pathogenesis of asthma, we and other groups have shown that IL-22 is involved in the regulation of allergic airway inflammation. In this review, we discuss recent advances in the biology of IL-22 and its involvement in the pathogenesis of allergic airway inflammation.
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Affiliation(s)
- Takashi Ito
- Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan; Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences (IMS), Kanagawa, Japan
| | - Koichi Hirose
- Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan; Department of Rheumatology, School of Medicine, International University of Health and Welfare, Chiba, Japan
| | - Hiroshi Nakajima
- Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
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Che F, Du H, Wei J, Zhang W, Cheng Z, Tong Y. MicroRNA-323 suppresses nerve cell toxicity in cerebral infarction via the transforming growth factor-β1/SMAD3 signaling pathway. Int J Mol Med 2018; 43:993-1002. [PMID: 30535466 DOI: 10.3892/ijmm.2018.4020] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2017] [Accepted: 10/19/2018] [Indexed: 11/06/2022] Open
Abstract
In the present study, the aim was to investigate the function of microRNA‑323 (miR‑323) in cerebral infarction and its underlying mechanism. A rat model of cerebral infarction was established and hippocampal tissues were analyzed. In addition, to further understand the role of miR‑323, PC12 cells were transfected with miR‑323 mimics or inhibitors and subjected to hypoxia to model cerebral infarction. Reverse transcription‑quantitative polymerase chain reaction was used to measure the expression of miR‑323. A luciferase reporter assay was conducted to analyze miR‑323 target sites the partial sequence of the 3'‑untranslated region of SMAD3 mRNA in vitro. Western blot analysis was also used to analyze transforming growth factor‑β1 (TGF‑β1) and SMAD3 protein expression levels. It was observed that miR‑323 expression was significantly upregulated in rats with cerebral infarction compared with rats in the sham‑control group. In addition, overexpression of miR‑323 induced nerve cell toxicity and reduced nerve cell growth in an in vitro model of cerebral infarction, whereas downregulation of miR‑323 caused the opposite effects on nerve cell toxicity and growth in this model. In addition, overexpression of miR‑323 directly targeted and suppressed SMAD3 expression in the in vitro model of cerebral infarction, while inhibition of miR‑323 induced SMAD3 expression. The use of a SMAD3 inhibitor suppressed the effect of anti‑miR‑323 on nerve cell toxicity in the in vitro model of cerebral infarction. Collectively, these findings suggested that miR‑323 suppresses nerve cell apoptosis in cerebral infarction via the TGF‑β1/SMAD3 signaling pathway.
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Affiliation(s)
- Fengli Che
- Department of Neurology, Beijing Luhe Hospital Capital Medical University, Beijing 101145, P.R. China
| | - Huishan Du
- Department of Neurology, Beijing Luhe Hospital Capital Medical University, Beijing 101145, P.R. China
| | - Jianchao Wei
- Department of Neurology, Beijing Luhe Hospital Capital Medical University, Beijing 101145, P.R. China
| | - Weidong Zhang
- Department of Neurology, Beijing Luhe Hospital Capital Medical University, Beijing 101145, P.R. China
| | - Zhe Cheng
- Department of Neurology, Beijing Luhe Hospital Capital Medical University, Beijing 101145, P.R. China
| | - Yanna Tong
- Department of Neurology, Beijing Luhe Hospital Capital Medical University, Beijing 101145, P.R. China
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Chen Y, Mao ZD, Shi YJ, Qian Y, Liu ZG, Yin XW, Zhang Q. Comprehensive analysis of miRNA-mRNA-lncRNA networks in severe asthma. Epigenomics 2018; 11:115-131. [PMID: 30426778 DOI: 10.2217/epi-2018-0132] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
AIM This study aimed to explore the molecular mechanism of severe asthma. MATERIALS & METHODS The shared and divergent differentially expressed mRNAs (DEmRNAs), miRNAs (DEmiRNAs) and lncRNAs (DElncRNAs) in asthma and severe asthma were identified by RNA-sequencing. Severe asthma-specific and shared DEmiRNA-DEmRNA-DElncRNA interaction networks were performed. RESULTS Compared with normal control, 1328 DEmRNAs, 608 DElncRNAs and 63 DEmiRNAs were identified in severe asthma. Compared with asthma, 95 DEmRNAs, 143 DElncRNAs and 96 DEmiRNAs were identified in severe asthma. MiR-133a-3p-EFHD2/CNN2-AC144831.1 interactions and miR-3613-3p-CD44/BCL11B-LINC00158/CTA-217C2.1/AC010976.2/RP11-641A6.2 interactions were speculated to involve with the development of severe asthma. The results of GSE69683 validation were generally consistent with our RNA-sequencing results. CONCLUSION This study provides clues for understanding the mechanism of severe asthma.
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Affiliation(s)
- Yi Chen
- Department of Respiratory and Critical Care Medicine, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, 29 Xinlong Road, Changzhou 213003, PR China
| | - Zheng-Dao Mao
- Department of Respiratory and Critical Care Medicine, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, 29 Xinlong Road, Changzhou 213003, PR China
| | - Yu-Jia Shi
- Department of Respiratory and Critical Care Medicine, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, 29 Xinlong Road, Changzhou 213003, PR China
| | - Yan Qian
- Department of Respiratory and Critical Care Medicine, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, 29 Xinlong Road, Changzhou 213003, PR China
| | - Zhi-Guang Liu
- Department of Respiratory and Critical Care Medicine, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, 29 Xinlong Road, Changzhou 213003, PR China
| | - Xiao-Wei Yin
- Department of Respiratory and Critical Care Medicine, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, 29 Xinlong Road, Changzhou 213003, PR China
| | - Qian Zhang
- Department of Respiratory and Critical Care Medicine, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, 29 Xinlong Road, Changzhou 213003, PR China
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Fekonja S, Korošec P, Rijavec M, Jeseničnik T, Kunej T. Asthma MicroRNA Regulome Development Using Validated miRNA-Target Interaction Visualization. OMICS-A JOURNAL OF INTEGRATIVE BIOLOGY 2018; 22:607-615. [PMID: 30124362 DOI: 10.1089/omi.2018.0112] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Asthma is a common multifactorial complex disease caused by an interaction of genetic and environmental factors. There are no robust biomarkers or molecular diagnostics for asthma or its detailed phenotypic stratification in the clinic. Regulatory and epigenomic factors are priority candidates for asthma biomarker discovery and translational research because this common disease emerges in association with host/environment interactions. In this context, epigenomic molecular events such as microRNA (miRNA) silencing affect asthma susceptibility and severity. We report here an analysis of the miRNAs in the literature, their targets associated with asthma, and present the findings organized as an miRNA-target network, an miRNA regulome of asthma. The miRNA-target interactions in asthma were extracted from the PubMed and the Web of Science databases, while the miRNA-target network was visualized with the Cytoscape tool. Genomic locations of miRNA and target genes were displayed using the Ensembl Whole Genome tool. We cataloged miRNAs associated with asthma and their experimentally validated targets, retrieving 48 miRNAs associated with asthma, and 54 experimentally validated miRNA targets. Four central molecules involved in 34.5% of all interactions were identified in the network. The miRNA-target pairs were constructed as an asthma-associated miRNA-target regulatory network. The network revealed subnetworks pointing toward potential asthma biomarker candidates. The asthma miRNA regulome reported here offers a strong foundation for future translational research and systems medicine applications for asthma diagnostic and therapeutic innovation. Developed protocol for constructing miRNA regulome could now be used for biomarker development in multifactorial diseases.
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Affiliation(s)
- Simon Fekonja
- 1 Department of Animal Science, Biotechnical Faculty, University of Ljubljana , Domžale, Slovenia
| | - Peter Korošec
- 2 Laboratory for Clinical Immunology and Molecular Genetics, University Clinic of Respiratory and Allergic Diseases Golnick, Golnik, Slovenia
| | - Matija Rijavec
- 2 Laboratory for Clinical Immunology and Molecular Genetics, University Clinic of Respiratory and Allergic Diseases Golnick, Golnik, Slovenia
| | - Taja Jeseničnik
- 3 Agronomy Department, Biotechnical Faculty, University of Ljubljana , Jamnikarjeva, Ljubljana, Slovenia
| | - Tanja Kunej
- 1 Department of Animal Science, Biotechnical Faculty, University of Ljubljana , Domžale, Slovenia
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Li HM, Xiao YJ, Min ZS, Tan C. Identification and interaction analysis of key genes and microRNAs in atopic dermatitis by bioinformatics analysis. Clin Exp Dermatol 2018; 44:257-264. [PMID: 29974487 DOI: 10.1111/ced.13691] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/02/2018] [Indexed: 12/11/2022]
Abstract
BACKGROUND Atopic dermatitis (AD) is a skin disease that carries a major health burden, but the exact mechanism of the disease is not yet known. AIM To identify the key genes and micro (mi)RNAs in AD, and to explore their potential molecular mechanisms. METHODS From the Gene Expression Omnibus (GEO) database, we downloaded microarray data for GSE32924 (mRNA profile) and GSE31408 (miRNA profile), which were analysed using GEO2R. Functional and pathway enrichment analyses were performed using the DAVID database, and the protein-protein interaction network was constructed with Cytoscape software. In addition, targets of differentially expressed miRNAs (DEMs) were predicted by the online resource miRDB. RESULTS In total, 328 differentially expressed genes (DEGs) were identified, including 121 upregulated and 207 downregulated genes. Gene Ontology analyses showed that upregulated genes were significantly enriched in immune responses, while downregulated genes were mainly involved in epidermis development. In addition, we identified three DEMs, all of which were downregulated. Hsa-let-7a-5p may target CCR7, and hsa-miR-26a-5p probably targets HAS3. CONCLUSIONS We identified lists of DEGs and DEMs in AD. Bioinformatics and interaction analysis may provide new clues for further studies of AD.
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Affiliation(s)
- H M Li
- Department of Dermatology, The Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China
| | - Y J Xiao
- Beijing ZhiYuanZhongHe Technology Co. Ltd., Beijing, China
| | - Z S Min
- Department of Dermatology, The Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China
| | - C Tan
- Department of Dermatology, The Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China
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The Clinical Significance of Changes in the Expression Levels of MicroRNA-1 and Inflammatory Factors in the Peripheral Blood of Children with Acute-Stage Asthma. BIOMED RESEARCH INTERNATIONAL 2018; 2018:7632487. [PMID: 30046607 PMCID: PMC6038680 DOI: 10.1155/2018/7632487] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/26/2018] [Revised: 04/18/2018] [Accepted: 05/07/2018] [Indexed: 12/21/2022]
Abstract
This study assessed the changes and clinical significance of microRNA-1 (miR-1) and inflammatory factors in the peripheral blood of children with acute-stage asthma. 100 children with acute-stage asthma (study group) and 100 healthy children (control group) were enrolled. For all enrolled children, the peripheral blood levels of miR-1, interleukin-4 (IL-4), IL-5, IL-8, tumor necrosis factor-alpha (TNF-α), and interferon-γ (IFN-γ) were measured. The relative expression levels of miR-1 and IFN-γ in the peripheral blood of children in the study group were significantly lower than those in the control group, whereas expression levels of IL-4, IL-5, IL-8, and TNF-α were significantly higher. Moreover, these levels changed to a greater extent in patients with severe disease (P < 0.05). Further analyses showed that the miR-1 expression level positively correlated with IFN-γ and negatively correlated with IL-4, IL-5, IL-8, and TNF-α expression levels (P < 0.05). ROC curve analysis to identify diagnostic specificity and sensitivity showed that, for diagnosing exacerbation in asthma, the area under the curve (AUC) for miR-1 was the highest (AUC = 0.900, P < 0.05) of all tested markers; this held true for diagnosing severe asthma as well (AUC = 0.977, P < 0.05). Compared to healthy children, children with acute-stage asthma had a low miR-1 expression level and a Th1/Th2 imbalance in their peripheral blood. The changes were closely related, became more exaggerated with an increase in disease severity, and could be used as auxiliary variables for diagnosing asthma exacerbation and evaluating disease severity.
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Inácio DP, Amado T, Silva-Santos B, Gomes AQ. Control of T cell effector functions by miRNAs. Cancer Lett 2018; 427:63-73. [PMID: 29679611 DOI: 10.1016/j.canlet.2018.04.011] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2018] [Revised: 03/23/2018] [Accepted: 04/10/2018] [Indexed: 12/12/2022]
Abstract
The differentiation of effector T cells is a tightly regulated process that relies on the selective expression of lineage-defining master regulators that orchestrate unique transcriptional programs, including the production of distinct sets of effector cytokines. miRNAs are post-transcriptional regulators that are now viewed as critical players in these gene expression networks and help defining cell identity and function. This review summarises the role of individual miRNAs in the regulation of the differentiation of effector T cell subsets, including CD4+ T helper cells, cytotoxic CD8+ T cells and innate-like NKT cells. Moreover, we refer to miRNAs that have been identified to affect simultaneously two or more effector T cell populations, impacting on the balance between effector T cells in vivo, thus constituting potential biomarkers or targets for therapies aiming at boosting immunity or controlling autoimmunity.
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Affiliation(s)
- Daniel P Inácio
- Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028, Lisboa, Portugal
| | - Tiago Amado
- Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028, Lisboa, Portugal
| | - Bruno Silva-Santos
- Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028, Lisboa, Portugal
| | - Anita Q Gomes
- Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028, Lisboa, Portugal; Escola Superior de Tecnologia da Saúde de Lisboa, 1990-096, Lisboa, Portugal.
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Yan S, Chen L, Zhao Q, Liu YN, Hou R, Yu J, Zhang H. Developmental endothelial locus-1 (Del-1) antagonizes Interleukin-17-mediated allergic asthma. Immunol Cell Biol 2018; 96:526-535. [PMID: 29437247 DOI: 10.1111/imcb.12023] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2017] [Revised: 02/08/2018] [Accepted: 02/08/2018] [Indexed: 01/13/2023]
Abstract
Interleukin (IL)-17 is a major contributor to the pathogenesis of allergic asthma. Developmental endothelial locus-1 (Del-1) is an endothelial cell-secreted protein known to inhibit IL-17 expression. However, little is known about the association between Del-1 and IL-17 in the pathogenesis of allergic asthma. Using bronchoalveolar lavage fluid (BALF) and peripheral blood samples collected from allergic asthmatic patients and controls, we explored the role of Del-1 in relation to IL-17 in allergic asthma. We found that the negative correlation between Del-1 and IL-17 was significant in BALF of allergic asthmatics. Del-1 treatment inhibited the expression of IL-17, the differentiation of IL-17-secreting leukocytes and associated cytokines. Contrarily, IL-17 levels were increased after treatment with anti-Del-1 mAb. Consistent with this, Del-1 treatment led to downregulation of IL-5, CCL5 and IL-4, thus reducing secretion of eosinophil cationic protein. Furthermore, Del-1 significantly downregulated the expression of ICAM-1 and may have the potential to reduce leukocyte transendothelial migration. Our data demonstrate that Del-1 can negatively regulate IL-17 and its proinflammatory function, thereby limiting airway inflammation in allergic asthmatics, and suggest Del-1 as a potential candidate for prevention and treatment of allergic asthma.
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Affiliation(s)
- Shu Yan
- Department of Clinical Laboratory, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Li Chen
- Department of Clinical Laboratory, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Qi Zhao
- Department of Clinical Laboratory, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Ya-Nan Liu
- Department of Clinical Laboratory, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Rui Hou
- Department of Clinical Laboratory, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Jing Yu
- Department of Clinical Laboratory, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Hong Zhang
- Department of Clinical Laboratory, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China
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Abstract
PURPOSE OF REVIEW MicroRNAs (miRNAs) are short, single-stranded, non-coding RNAs that are increasingly being recognized as important epigenetic regulators. They have been implicated in the pathogenesis of many diseases including cancer, cardiovascular diseases, connective tissue diseases, and neuromuscular disorders. RECENT FINDINGS A few miRNAs have already been recognized as a core set of miRNAs important in allergic inflammation. These include let-7, miR-21, miR-142, and miR-146. This review aims to bring together some of the recent findings on how miRNAs regulate allergic inflammation with special focus on asthma, atopic dermatitis, allergic rhinitis, and eosinophilic esophagitis. We will also touch upon extracellular miRNAs and future perspective of this field of study.
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Affiliation(s)
- Eishika Dissanayake
- Department of Pediatrics, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, Chiba, 260-8670, Japan
| | - Yuzaburo Inoue
- Department of General Medical Science, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, Chiba, 260-8670, Japan.
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Cui D, Zhong F, Lin J, Wu Y, Long Q, Yang X, Zhu Q, Huang L, Mao Q, Huo Z, Zhou Z, Xie G, Zheng S, Yu F, Chen Y. Changes of circulating Th22 cells in children with hand, foot, and mouth disease caused by enterovirus 71 infection. Oncotarget 2017; 8:29370-29382. [PMID: 28030850 PMCID: PMC5438737 DOI: 10.18632/oncotarget.14083] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2016] [Accepted: 12/16/2016] [Indexed: 12/17/2022] Open
Abstract
Interleukin (IL)-22+CD4+T (Th22) cells play crucial roles in the pathogenesis of autoimmune diseases and infectious diseases, although the role of Th22 cells remains largely unclear in children with hand, foot, and mouth disease (HFMD) caused by enterovirus 71 (EV71). This study aims to explore the role of circulating IL-22+IL-17A-CD4+T (cTh22) cells in children with EV71-associated HFMD. We found that during the acute stage of illness, the frequencies of cTh22 and circulating IL-22+IL-17A+CD4+T (IL-22+cTh17) cells in CD4+T cells infrom affected patients, and especially in severely affected patients, were significantly higher than in healthy controls (HC). The major source of IL-22 production was cTh22 cells, partially from cTh17 cells. Moreover, the protein and mRNA levels of IL-22, IL-17A, IL-23, IL-6, and TNF-α were significantly different among the mild patients, severe patients and HC, as well as AHR and RORγt mRNA levels. A positive correlation was found between plasma IL-22 levels and cTh22 cell frequencies, and cTh17 cell and IL-22+ cTh17 cell frequencies. Furthermore, the frequencies of cTh22 were significantly decreased in the convalescent patients. Our findings indicated that cTh22 cells could play critical roles in the pathogenesis of EV71 infection, and are potential therapeutic targets for patients with EV71-associated HFMD.
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Affiliation(s)
- Dawei Cui
- Department of Laboratory Medicine, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
- Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, Hangzhou, China
| | - Fengyun Zhong
- Department of General Surgery, the Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Jie Lin
- Department of Clinical Laboratory, Center of Community Health Service of Qingbo Street, Hangzhou, China
| | - Yidong Wu
- Clinical Laboratory, Hangzhou Children’s Hospital, Hangzhou, China
| | - Quan Long
- Department of Laboratory Medicine, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
- Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, Hangzhou, China
| | - Xianzhi Yang
- Department of Laboratory Medicine, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
- Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, Hangzhou, China
| | - Qiaoyun Zhu
- Department of Laboratory Medicine, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
- Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, Hangzhou, China
| | - Li Huang
- Department of Laboratory Medicine, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
- Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, Hangzhou, China
| | - Qifen Mao
- Department of Laboratory Medicine, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
- Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, Hangzhou, China
| | - Zhaoxia Huo
- Department of Laboratory Medicine, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
- Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, Hangzhou, China
| | - Zhe Zhou
- Department of Laboratory Medicine, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
- Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, Hangzhou, China
| | - Guoliang Xie
- Department of Laboratory Medicine, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
- Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, Hangzhou, China
| | - Shufa Zheng
- Department of Laboratory Medicine, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
- Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, Hangzhou, China
| | - Fei Yu
- Department of Laboratory Medicine, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
- Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, Hangzhou, China
| | - Yu Chen
- Department of Laboratory Medicine, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
- Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, Hangzhou, China
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Zhang J, Zhou Z, Zhang N, Jin W, Ren Y, Chen C. Establishment of preliminary regulatory network of TRPV1 and related cytokines. Saudi J Biol Sci 2017; 24:582-588. [PMID: 28386183 PMCID: PMC5372391 DOI: 10.1016/j.sjbs.2017.01.029] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2016] [Revised: 12/28/2016] [Accepted: 01/07/2017] [Indexed: 11/23/2022] Open
Abstract
Our purpose was to investigate the regulatory mechanism of TRPV1 and related cytokines on children bronchial asthma. TRPV1 mRNA level and two SNP genotypes of children in case group and control group were detected by real-time quantitative PCR. Western blot and ELISA were used to measure the levels of cytokines like IgE, IL-2, etc. Their correlations were analyzed by Logistic regression and KEGG analysis. Moreover, tertiary structure of protein and miRNA binding sites were also predicted by online tools. Case group was obviously different from control group in TRPV1 mRNA level, the two SNP genotypes distribution and the related cytokines levels. Logistic regression analysis further demonstrated that TRPV1 mRNA level, EOS, IL-4 and IL-5 may be risk factors for children bronchial asthma. And based on that, the preliminary regulatory network of children bronchial asthma was drawn. What’s more, mutation of rs4790521 and rs4790522 in TRPV1 gene both induced its corresponding miRNA binding site’s change. The preliminary regulatory network of TRPV1 and related cytokines on children bronchial asthma established in this study provides certain theoretical basis for pathogenesis and treatment of children bronchial asthma.
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Affiliation(s)
- Jianhua Zhang
- Medical Engineering Technology and Data Mining Institute of Zhengzhou University, No. 100 Science Ave., Gaoxin Dist., Zhengzhou 450001, China
| | - Zheng Zhou
- Department of Respiration, The Second Affiliated Hospital of Zhengzhou University, No. 2 Jingba Rd., Zhengzhou 450014, China
| | - Ning Zhang
- Medical Engineering Technology and Data Mining Institute of Zhengzhou University, No. 100 Science Ave., Gaoxin Dist., Zhengzhou 450001, China
| | - Wenwen Jin
- Medical Engineering Technology and Data Mining Institute of Zhengzhou University, No. 100 Science Ave., Gaoxin Dist., Zhengzhou 450001, China
| | - Yafeng Ren
- Department of Chinese Internal Medicine, The First Affiliated Hospital of Zhengzhou University, No. 1 East Jianshe Rd., Zhengzhou 450052, China
| | - Chuanliang Chen
- Hospital Office, People's Hospital of Zhengzhou University, No. 7 Weiwu Rd., Zhengzhou 450003, China
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Cohen TS. Role of MicroRNA in the Lung's Innate Immune Response. J Innate Immun 2016; 9:243-249. [PMID: 27915347 DOI: 10.1159/000452669] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2016] [Accepted: 10/18/2016] [Indexed: 12/22/2022] Open
Abstract
The immune response to respiratory pathogens must be robust enough to defend the host yet properly constrained such that inflammation-induced tissue damage is avoided. MicroRNA (miRNA) are small noncoding RNA which posttranscriptionally influence gene expression. In this review, we discuss recent experimental evidence of the contribution of miRNA to the lung's response to bacterial and viral pathogens.
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Affiliation(s)
- Taylor S Cohen
- Department of Infectious Disease, Medimmune, Gaithersburg, MD, USA
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