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Lada G. Immune links in comorbid depression and psoriasis: A narrative mini-review and perspective. Brain Behav Immun Health 2025; 44:100949. [PMID: 39959848 PMCID: PMC11830344 DOI: 10.1016/j.bbih.2025.100949] [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: 11/29/2023] [Revised: 12/19/2024] [Accepted: 01/13/2025] [Indexed: 02/18/2025] Open
Abstract
Evidence suggests a bidirectional association between psoriasis and depression, which is considered to reflect complex neuroimmunological and psychosocial interactions. Despite an early interest in the brain-skin axis and the role of stress in psoriasis immunopathogenesis, there is ongoing limited preclinical and clinical research into the inflammatory links between depression and psoriasis. Existing findings for serum inflammatory markers of depression in psoriasis are inconsistent and do not fully align with those in the general population, while brain imaging evidence is scarce and has not confirmed direct brain involvement in the systemic inflammation of psoriasis. The present paper reviews the available literature on the immune interplay of psoriasis with depression, highlights the significance of further work in the field and proposes avenues for future research.
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Affiliation(s)
- Georgia Lada
- Dermatology Centre, Northern Care Alliance NHS Foundation Trust, Manchester Academic Health Science Centre, Division of Musculoskeletal & Dermatological Sciences, The University of Manchester, Greater Manchester M6 8HD, United Kingdom
- Greater Manchester Mental Health NHS Foundation Trust, Greater Manchester, United Kingdom
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Wang Y, Li D, Yan Z, Shi D. Immunoglobulin E, the potential accelerator of comorbid psoriasis and atherosclerosis. Biomed Pharmacother 2025; 183:117860. [PMID: 39848109 DOI: 10.1016/j.biopha.2025.117860] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2024] [Revised: 01/12/2025] [Accepted: 01/18/2025] [Indexed: 01/25/2025] Open
Abstract
Immunoglobulin (Ig) E is a key mediator in the induction and maintenance of allergic inflammation, characterized by a Th2-dominated immune response. Recently epidemiological studies have showed that elevated serum total IgE levels or an increased abundance of mast cells (MCs) at the lesion site are observed in psoriatic patients with cardiovascular diseases (CVD), such as atherosclerosis. Although the underlying mechanisms by which IgE synergizing with MCs in promoting these chronic immune-inflammatory diseases remain unclear, the interleukin (IL)-23/IL-17 axis appears to play a crucial role in comorbidity of psoriasis and atherosclerosis. High IgE production may result from IL-17A response, further exacerbating inflammatory pathways involved in both psoriasis and atherosclerosis. This review explores the possible mechanisms of IgE in these comorbid conditions, reinforcing the rationale for IL-17A targeted biologics in the treatment of psoriasis and atherosclerosis comorbidity. Additionally, IgE is proposed as a potential therapeutic target for alleviating patients suffering from these comorbidity conditions.
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Affiliation(s)
- Yan Wang
- Department of Neurology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Dongmei Li
- Department of Microbiology & Immunology, Georgetown University Medical Center, Washington DC, United States
| | - Zhongrui Yan
- Department of Neurology, Jining No.1 People's Hospital affiliated to Shandong First Medical University, Jining, Shandong, China.
| | - Dongmei Shi
- Laboratory of Medical Mycology & Department of Dermatology, Jining No.1 People's Hospital affiliated to Shandong First Medical University, Jining, Shandong, China.
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Korhonen J, Siiskonen H, Haimakainen S, Harvima RJ, Harvima IT. Expression of mast cell tryptase and immunoglobulin E is increased in cutaneous photodamage: implications for carcinogenesis. J DERMATOL TREAT 2024; 35:2307488. [PMID: 38291602 DOI: 10.1080/09546634.2024.2307488] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2023] [Accepted: 01/15/2024] [Indexed: 02/01/2024]
Abstract
Purpose: Mast cells, their serine proteinase tryptase, and immunoglobulin E (IgE) can be involved in cutaneous carcinogenesis.Materials and methods: To study the association of tryptase+ and IgE+ cells with photodamage and skin cancers 385 adult patients (201 males, 184 females, 75 with immunosuppression) at risk of any type of skin cancer were examined. Skin biopsies were taken from the sun-protected medial arm and from the photodamaged dorsal forearm skin followed by immunohistochemical staining for tryptase and IgE.Results: The results show that tryptase+ and IgE+ cells are significantly higher in number in the photodamaged than sun-protected skin, both in immunocompetent and -compromised subjects, and there is a strong correlation between tryptase+ and IgE+ cells. The numbers of forearm tryptase+ and especially IgE+ cells associated significantly with the forearm photodamage severity. In the logistic regression analysis, the forearm to upper arm ratio of IgE+ cells produced a univariate odds ratio of 1.521 (p = .010) and a multivariate one of 3.875 (p = .047) for the history of squamous cell carcinoma. The serum level of total IgE correlated significantly to the IgE to tryptase ratio in both skin sites.Conclusions: Therefore, IgE+ mast cells participate in photodamage and carcinogenesis, though it is unclear whether they are tumor-protective or -causative.
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Affiliation(s)
- Jenni Korhonen
- Department of Dermatology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland
| | - Hanna Siiskonen
- Department of Dermatology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland
| | - Salla Haimakainen
- Department of Dermatology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland
| | - Rauno J Harvima
- Department of Dermatology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland
| | - Ilkka T Harvima
- Department of Dermatology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland
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Bezzio C, Cavalli CAM, Franchellucci G, Dal Buono A, Gabbiadini R, Scalvini D, Manara S, Narcisi A, Armuzzi A, Saibeni S. Psoriasis and inflammatory bowel disease: concomitant IMID or paradoxical therapeutic effect? A scoping review on anti-IL-12/23 and anti-IL-23 antibodies. Therap Adv Gastroenterol 2024; 17:17562848241299564. [PMID: 39575159 PMCID: PMC11580083 DOI: 10.1177/17562848241299564] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2024] [Accepted: 10/18/2024] [Indexed: 11/24/2024] Open
Abstract
Inflammatory bowel diseases (IBD) and psoriasis are chronic inflammatory conditions belonging to the heterogeneous group of immune-mediated inflammatory diseases (IMIDs). A significant bidirectional link between these two entities has been observed, conditioning an increased risk of IBD in patients with psoriasis and vice-versa. Biological therapies used for IBD may lead to the occurrence of psoriasis as a "paradoxical reaction." The objective of this study is to analyze the current evidence on the association between psoriasis and IBD, particularly finding case reports of the appearance or aggravation of psoriasis under therapy with interleukin-12/23 (IL-12/23) and IL-23 inhibitors. We conducted comprehensive research to identify studies examining the association between psoriasis and IBD and to find case presentations that reported the appearance or aggravation of psoriasis under biologic therapy with IL-12/23 and IL-23 inhibitors up to March 2024. Clinical trials for IL-12/23 and IL-23 inhibitors in IBD were analyzed to find cases of paradoxical psoriasis as registered adverse events. The sources of evidence are PubMed and ClinicalTrials.gov. For each included case report, data on patient characteristics concerning their age, sex, and comorbidities were selected. Moreover, information regarding the indication for biologic therapy, time to onset of paradoxical psoriasis after starting treatment, clinical presentation, and management of the paradoxical psoriasis was extracted. We found 10 reported cases of ustekinumab-induced new-onset or worsening psoriasis and one reported case of paradoxical psoriasis induced by risankizumab in the literature. Four cases of paradoxical psoriasis have been also registered in clinical trials involving ustekinumab treatment in IBD. Psoriasis can constitute a rare paradoxical adverse event of ustekinumab treatment, but further studies are needed to better clarify the cytokine imbalance that leads to this phenomenon induced by inhibition of IL-12/23 and IL-23. Still, few real-world data exist to draw any conclusions, but risankizumab may positively treat psoriasis induced by ustekinumab.
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Affiliation(s)
- Cristina Bezzio
- IBD Centre, IRCCS Humanitas, Research Hospital, Rozzano, Lombardia 20089, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
| | - Carolina Aliai Micol Cavalli
- Gastroenterology and Digestive Endoscopy Unit, Santa Maria degli Angeli Hospital, Azienda Sanitaria Friuli Occidentale, Pordenone, Italy
| | | | - Arianna Dal Buono
- IBD Centre, IRCCS Humanitas Research Hospital, Rozzano, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
| | | | - Davide Scalvini
- Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy
| | - Sofia Manara
- Department of Pathology, IRCCS Humanitas Research Hospital, Rozzano, Italy
| | | | - Alessandro Armuzzi
- IBD Centre, IRCCS Humanitas Research Hospital, Rozzano, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
| | - Simone Saibeni
- IBD Centre, Gastroenterology Unit, Rho Hospital, ASST Rhodense, Rho, Italy
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5
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Alsabbagh MM. Cytokines in psoriasis: From pathogenesis to targeted therapy. Hum Immunol 2024; 85:110814. [PMID: 38768527 DOI: 10.1016/j.humimm.2024.110814] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2024] [Revised: 05/14/2024] [Accepted: 05/15/2024] [Indexed: 05/22/2024]
Abstract
Psoriasis is a multifactorial disease that affects 0.84% of the global population and it can be associated with disabling comorbidities. As patients present with thick scaly lesions, psoriasis was long believed to be a disorder of keratinocytes. Psoriasis is now understood to be the outcome of the interaction between immunological and environmental factors in individuals with genetic predisposition. While it was initially thought to be solely mediated by cytokines of type-1 immunity, namely interferon-γ, interleukin-2, and interleukin-12 because it responds very well to cyclosporine, a reversible IL-2 inhibitor; the discovery of Th-17 cells advanced the understanding of the disease and helped the development of biological therapy. This article aims to provide a comprehensive review of the role of cytokines in psoriasis, highlighting areas of controversy and identifying the connection between cytokine imbalance and disease manifestations. It also presents the approved targeted treatments for psoriasis and those currently under investigation.
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Affiliation(s)
- Manahel Mahmood Alsabbagh
- Princess Al-Jawhara Center for Molecular Medicine and Inherited Disorders and Department of Molecular Medicine, Arabian Gulf University, Manama, Bahrain.
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Gheorghe SR, Ilyés T, Filip GA, Dănescu AS, Timiș TL, Orăsan M, Stamate I, Crăciun AM, Silaghi CN. Low Vitamin K Status in Patients with Psoriasis Vulgaris: A Pilot Study. Biomedicines 2024; 12:1180. [PMID: 38927387 PMCID: PMC11200760 DOI: 10.3390/biomedicines12061180] [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: 04/26/2024] [Revised: 05/22/2024] [Accepted: 05/24/2024] [Indexed: 06/28/2024] Open
Abstract
Psoriasis vulgaris (PV) is a disease characterized by skin manifestations and systemic inflammation. There are no published studies to date on vitamin K status assessed by extrahepatic vitamin K-dependent proteins [e.g., osteocalcin (OC) and matrix Gla protein (MGP)] in patients with PV, even if vitamin K was found to promote wound contraction and decrease the healing time of the skin. Metabolic syndrome (MS), a comorbidity of PV, was found to influence vitamin K status, and vitamin D was found to be involved in the pathogenesis of PV. Therefore, our aim was to assess the status of vitamins K and D in subjects with PV. We enrolled 44 patients with PV and 44 age- and sex-matched subjects as a control group (CG), of which individuals with MS were designated the CG with MS subgroup. Furthermore, the PV patients were stratified into two subgroups: those with MS (n = 20) and those without MS (n = 24). In addition to the quantification of vitamin D and MGP in all subjects, the uncarboxylated OC/carboxylated OC (ucOC/cOC) ratio was also assessed as an inversely proportional marker of vitamin K status. We found an increased ucOC/cOC ratio in the PV group compared to CG but also a greater ucOC/cOC ratio in the PV with MS subgroup than in the CG with MS subgroup. MGP was decreased in the PV with MS subgroup compared to CG with MS subgroup. There was no difference in the vitamin D concentration between the groups. This is the first study to report decreased vitamin K status in patients with PV, independent of the presence of MS.
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Affiliation(s)
- Simona R. Gheorghe
- Department of Medical Biochemistry, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania; (S.R.G.); (T.I.); (C.N.S.)
| | - Tamás Ilyés
- Department of Medical Biochemistry, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania; (S.R.G.); (T.I.); (C.N.S.)
| | - Gabriela A. Filip
- Department of Physiology, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania; (G.A.F.); (T.L.T.)
| | - Ana S. Dănescu
- Department of Dermatology, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania;
| | - Teodora L. Timiș
- Department of Physiology, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania; (G.A.F.); (T.L.T.)
| | - Meda Orăsan
- Department of Physiopathology, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania;
| | - Irina Stamate
- Centre Neuchatelois de Psychiatrie, 2000 Neuchâtel, Switzerland;
| | - Alexandra M. Crăciun
- Department of Medical Biochemistry, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania; (S.R.G.); (T.I.); (C.N.S.)
| | - Ciprian N. Silaghi
- Department of Medical Biochemistry, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania; (S.R.G.); (T.I.); (C.N.S.)
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Rahkola D, Harvima RJ, Harvima IT. Increased expression of complement C3c, iC3b, and cells containing CD11b or CD14 in experimentally induced psoriatic lesion. Clin Exp Immunol 2024; 216:252-261. [PMID: 38310540 PMCID: PMC11097906 DOI: 10.1093/cei/uxae009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2023] [Revised: 11/08/2023] [Accepted: 02/02/2024] [Indexed: 02/06/2024] Open
Abstract
Psoriasis is a chronic inflammatory skin disease with a characteristic isomorphic reaction, i.e. the Köbner reaction, induced by slight epidermal trauma. In this study, the tape-stripping technique was used to induce the development of Köbner reaction in 18 subjects with psoriasis. Eight subjects developed a positive reaction. To study the early cellular changes, skin biopsies were taken at the baseline and subsequent time points of 2 h, 1 d, 3 d, and 7 d for the immunostaining of complement C3c, iC3b, and cells expressing complement receptor 3 (CD11b/CD18; a receptor of iC3b) or CD14. The results show that the positive Köbner reaction is associated with rapid (2 h-1 d) and sustained (3-7 d) increase in the expression of epidermal C3c and iC3b and dermal C3c. In addition, there was a positive correlation between CD11b+ and CD14+ cells in baseline and 2 h-1 d biopsies with a subsequent increase in CD11b+ and CD14+ cells in 3-7 d biopsies in the Köbner-positive group. In the Köbner-negative group, only a transient increase in epidermal iC3b at 2 h-1 d, as well as rapid (2 h-1 d) and sustained increase (3-7 d) in dermal iC3b and CD14+ cells, was observed. In experiments with cultured monolayer keratinocytes, a slight cell damage already at 30 mJ/cm2 ultraviolet B irradiation led to increased expression of C3c, but not iC3b. Therefore, there are marked differences between Köbner groups in respect to the expression of C3c, iC3b, and cells expressing CD11b or CD14. Of note is the rapid and sustained increase in epidermal C3c and iC3b in the positive Köbner reaction.
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Affiliation(s)
- Dina Rahkola
- Department of Dermatology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland
| | - Rauno J Harvima
- Department of Dermatology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland
| | - Ilkka T Harvima
- Department of Dermatology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland
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8
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Zhang L, Li X, Xu X, Le Y, Cao H, Zhang J, Xue F, Hu M, Xia Y, Pan M, Chen L, Zheng J. Ixekizumab-induced urticaria is associated with the short duration of remission in psoriasis by activation of mast cells. J Am Acad Dermatol 2024; 90:970-976. [PMID: 38244613 DOI: 10.1016/j.jaad.2024.01.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2023] [Revised: 01/05/2024] [Accepted: 01/06/2024] [Indexed: 01/22/2024]
Abstract
BACKGROUND Mast cell degranulation plays a pivotal role in urticaria and is also an early histologic characteristic of psoriasis. However, whether the activation of mast cells contributes to psoriasis recurrence after discontinuation of interleukin (IL)-17A blockers remains unclear. OBJECTIVE To investigate the role of mast cells in ixekizumab treatment-associated urticaria (ITAUR) and assess the effect of urticaria eruption on psoriasis relapse. METHODS A retrospective analysis was performed on biopsies of patients who experienced psoriasis relapse after discontinuation of ixekizumab. Transcriptomic and histopathologic features were assessed. Patterns were compared between patients with ITAUR and nonurticaria (NUR) as well as psoriasis-like mice with mast cell activation or inactivation. RESULTS Patients with ITAUR experienced early relapse compared with NUR group after treatment withdrawal. Transcriptomic and histopathologic analyses revealed that patients with ITAUR had an elevated proportion of mast cells in resolved skin. Especially, the proportion of IL-17A+ mast cells was inversely correlated with the duration of remission. LIMITATIONS The mechanism of mast cell activation in ITAUR has not been precisely elucidated. CONCLUSION Ixekizumab treatment increases IL-17A+ mast cells in lesions of ITAUR, which is associated with early psoriasis relapse after ixekizumab withdrawal.
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Affiliation(s)
- Li Zhang
- Laboratory of Dermatoimmunology, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Xia Li
- Department of Dermatology, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Xintian Xu
- Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Shanghai, China
| | - Yunchen Le
- Laboratory of Dermatoimmunology, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Han Cao
- Laboratory of Dermatoimmunology, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Jiayi Zhang
- Department of Dermatology, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Feng Xue
- Laboratory of Dermatoimmunology, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Mengyan Hu
- Department of Dermatology, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Yuhan Xia
- Laboratory of Dermatoimmunology, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Meng Pan
- Department of Dermatology, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Lihong Chen
- Department of Dermatology, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
| | - Jie Zheng
- Laboratory of Dermatoimmunology, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
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9
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Sieminska I, Pieniawska M, Grzywa TM. The Immunology of Psoriasis-Current Concepts in Pathogenesis. Clin Rev Allergy Immunol 2024; 66:164-191. [PMID: 38642273 PMCID: PMC11193704 DOI: 10.1007/s12016-024-08991-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/01/2024] [Indexed: 04/22/2024]
Abstract
Psoriasis is one of the most common inflammatory skin diseases with a chronic, relapsing-remitting course. The last decades of intense research uncovered a pathological network of interactions between immune cells and other types of cells in the pathogenesis of psoriasis. Emerging evidence indicates that dendritic cells, TH17 cells, and keratinocytes constitute a pathogenic triad in psoriasis. Dendritic cells produce TNF-α and IL-23 to promote T cell differentiation toward TH17 cells that produce key psoriatic cytokines IL-17, IFN-γ, and IL-22. Their activity results in skin inflammation and activation and hyperproliferation of keratinocytes. In addition, other cells and signaling pathways are implicated in the pathogenesis of psoriasis, including TH9 cells, TH22 cells, CD8+ cytotoxic cells, neutrophils, γδ T cells, and cytokines and chemokines secreted by them. New insights from high-throughput analysis of lesional skin identified novel signaling pathways and cell populations involved in the pathogenesis. These studies not only expanded our knowledge about the mechanisms of immune response and the pathogenesis of psoriasis but also resulted in a revolution in the clinical management of patients with psoriasis. Thus, understanding the mechanisms of immune response in psoriatic inflammation is crucial for further studies, the development of novel therapeutic strategies, and the clinical management of psoriasis patients. The aim of the review was to comprehensively present the dysregulation of immune response in psoriasis with an emphasis on recent findings. Here, we described the role of immune cells, including T cells, B cells, dendritic cells, neutrophils, monocytes, mast cells, and innate lymphoid cells (ILCs), as well as non-immune cells, including keratinocytes, fibroblasts, endothelial cells, and platelets in the initiation, development, and progression of psoriasis.
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Affiliation(s)
- Izabela Sieminska
- University Centre of Veterinary Medicine, University of Agriculture in Krakow, Krakow, Poland
| | - Monika Pieniawska
- Institute of Human Genetics, Polish Academy of Sciences, Poznań, Poland
| | - Tomasz M Grzywa
- Laboratory of Immunology, Mossakowski Medical Research Institute, Polish Academy of Sciences, Warsaw, Poland.
- Department of Methodology, Medical University of Warsaw, Warsaw, Poland.
- The Raymond G. Perelman Center for Cellular and Molecular Therapeutics, Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, USA.
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10
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Benezeder T, Bordag N, Woltsche J, Teufelberger A, Perchthaler I, Weger W, Salmhofer W, Gruber-Wackernagel A, Painsi C, Zhan Q, El-Heliebi A, Babina M, Clark R, Wolf P. Mast cells express IL17A, IL17F and RORC, are activated and persist with IL-17 production in resolved skin of patients with chronic plaque-type psoriasis. RESEARCH SQUARE 2024:rs.3.rs-3958361. [PMID: 38410434 PMCID: PMC10896398 DOI: 10.21203/rs.3.rs-3958361/v1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/28/2024]
Abstract
Little is known about IL-17 expression in psoriasis and the actual cellular source of IL-17 remains incompletely defined. We show that high numbers of IL-17 + mast cells persisted in resolved lesions after treatment (anti-IL-17A, anti-IL-23, UVB or topical dithranol) and correlated inversely with the time span in remission. IL-17 + mast cells were found in T cell-rich areas and often close to resident memory T cells (Trm) in active psoriasis and resolved lesional skin. Digital cytometry by deconvolution of RNA-seq data showed that activated mast cells were increased in psoriatic skin, while resting mast cells were almost absent and both returned to normal levels after treatment. When primary human skin mast cells were stimulated with T cell cytokines (TNFα, IL-22 and IFNγ), they responded by releasing more IL-17A, as measured by ELISA. In situ mRNA detection using padlock probes specific for transcript variants of IL17A, IL17F, and RORC (encoding the Th17 transcription factor RORγt) revealed positive mRNA signals for IL17A, IL17F, and RORCin tryptase + cells, demonstrating that mast cells have the transcriptional machinery to actively produce IL-17. Mast cells thus belong to the center of the IL-23/IL-17 axis and high numbers of IL-17 + mast cells predict an earlier disease recurrence.
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Affiliation(s)
- Theresa Benezeder
- Department of Dermatology and Venereology, Medical University of Graz
| | - Natalie Bordag
- Department of Dermatology and Venereology, Medical University of Graz
| | - Johannes Woltsche
- Department of Dermatology and Venereology, Medical University of Graz
| | | | | | - Wolfgang Weger
- Department of Dermatology and Venereology, Medical University of Graz
| | | | | | | | - Qian Zhan
- Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School
| | - Amin El-Heliebi
- Division of Cell Biology, Histology and Embryology, Gottfried Schatz Research Center, Medical University of Graz
| | - Magda Babina
- Institute of Allergology, Charite-Universitatsmedizin Berlin
| | | | - Peter Wolf
- Department of Dermatology and Venereology, Medical University of Graz, Graz, Austria
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11
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Soni B, Shivgotra R, Trehan K, Chhina A, Saini M, Jain SK, Thakur S. An Overview of Contemporary and Future Therapeutic Strategies for Scalp Psoriasis. Curr Drug Targets 2024; 25:353-373. [PMID: 38500274 DOI: 10.2174/0113894501292755240304063020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2023] [Revised: 02/06/2024] [Accepted: 02/12/2024] [Indexed: 03/20/2024]
Abstract
Scalp psoriasis is a common manifestation of psoriasis that significantly impacts a patient's quality of life. About 80% of cases of psoriasis involve the scalp, making it the most frequently affected area of the body. The treatment of scalp psoriasis is particularly crucial because of its hard-to-treat nature and substantial adverse impacts on overall well-being. Along with the physical symptoms of discomfort and itching, psoriasis, especially when it affects the scalp, can cause severe psychological damage. Treating scalp psoriasis can be challenging due to its location and associated symptoms, such as scaling and pruritus, which is why various drugs have become widely used for refractory cases. Topical treatments like corticosteroids and vitamin D analogs manage scalp psoriasis by reducing inflammation and regulating skin cell growth. Tar-based shampoos, salicylic acid solutions, and moisturizers control scaling. Phototherapy with UVB light reduces inflammation. Severe cases may require systemic medications such as oral retinoids and immunosuppressants. While various therapies are accessible for scalp psoriasis, concerns arise due to their limited advantages and the absence of controlled studies assessing their effectiveness. Considering these challenges, there is a clear demand for innovative approaches to address this condition effectively. Recent advancements in topical therapies, phototherapy, systemic agents, and complementary therapies have shown promising results in managing scalp psoriasis. Also, the advent of biologics, specifically anti-IL-17 and anti-IL-23 drugs for scalp psoriasis, has seen significant improvements. The review highlights the lack of well-tolerated and effective treatments for scalp psoriasis and underscores the importance of further research in this area. The objective of this review is to clarify the different treatment options currently available or being investigated in clinical trials for managing scalp psoriasis.
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Affiliation(s)
- Bindu Soni
- Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab, 143005, India
| | - Riya Shivgotra
- Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab, 143005, India
| | - Karan Trehan
- Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab, 143005, India
| | - Aashveen Chhina
- Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab, 143005, India
| | - Muskaan Saini
- Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab, 143005, India
| | - Subheet Kumar Jain
- Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab, 143005, India
- Centre for Basic and Translational Research in Health Sciences, Guru Nanak Dev University, Amritsar, 143005, India
| | - Shubham Thakur
- Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab, 143005, India
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12
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Joshi M, Hiremath P, John J, Ranadive N, Nandakumar K, Mudgal J. Modulatory role of vitamins A, B3, C, D, and E on skin health, immunity, microbiome, and diseases. Pharmacol Rep 2023; 75:1096-1114. [PMID: 37673852 PMCID: PMC10539462 DOI: 10.1007/s43440-023-00520-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2023] [Revised: 08/17/2023] [Accepted: 08/18/2023] [Indexed: 09/08/2023]
Abstract
Disruption of the skin barrier and immunity has been associated with several skin diseases, namely atopic dermatitis (AD), psoriasis, and acne. Resident and non-resident immune cells and the barrier system of the skin are integral to innate immunity. Recent advances in understanding skin microbiota have opened the scope of further understanding the various communications between these microbiota and skin immune cells. Vitamins, being one of the important micronutrients, have been reported to exert antioxidant, anti-inflammatory, and anti-microbial effects. The immunomodulatory action of vitamins can halt the progression of skin diseases, and thus, understanding the immuno-pharmacology of these vitamins, especially for skin diseases can pave the way for their therapeutic potential. At the same time, molecular and cellular markers modulated with these vitamins and their derivatives need to be explored. The present review is focused on significant vitamins (vitamins A, B3, C, D, and E) consumed as nutritional supplements to discuss the outcomes and scope of studies related to skin immunity, health, and diseases.
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Affiliation(s)
- Mahika Joshi
- Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, 576104, Karnataka, India
| | - Priyanka Hiremath
- Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, 576104, Karnataka, India
| | - Jeena John
- Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, 576104, Karnataka, India
| | - Niraja Ranadive
- Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, 576104, Karnataka, India
| | - Krishnadas Nandakumar
- Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, 576104, Karnataka, India
| | - Jayesh Mudgal
- Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, 576104, Karnataka, India.
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13
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Dileepan KN, Raveendran VV, Sharma R, Abraham H, Barua R, Singh V, Sharma R, Sharma M. Mast cell-mediated immune regulation in health and disease. Front Med (Lausanne) 2023; 10:1213320. [PMID: 37663654 PMCID: PMC10470157 DOI: 10.3389/fmed.2023.1213320] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Accepted: 07/17/2023] [Indexed: 09/05/2023] Open
Abstract
Mast cells are important components of the immune system, and they perform pro-inflammatory as well as anti-inflammatory roles in the complex process of immune regulation in health and disease. Because of their strategic perivascular localization, sensitivity and adaptability to the microenvironment, and ability to release a variety of preformed and newly synthesized effector molecules, mast cells perform unique functions in almost all organs. Additionally, Mast cells express a wide range of surface and cytoplasmic receptors which enable them to respond to a variety of cytokines, chemicals, and pathogens. The mast cell's role as a cellular interface between external and internal environments as well as between vasculature and tissues is critical for protection and repair. Mast cell interactions with different immune and nonimmune cells through secreted inflammatory mediators may also turn in favor of disease promoting agents. First and forefront, mast cells are well recognized for their multifaceted functions in allergic diseases. Reciprocal communication between mast cells and endothelial cells in the presence of bacterial toxins in chronic/sub-clinical infections induce persistent vascular inflammation. We have shown that mast cell proteases and histamine induce endothelial inflammatory responses that are synergistically amplified by bacterial toxins. Mast cells have been shown to exacerbate vascular changes in normal states as well as in chronic or subclinical infections, particularly among cigarette smokers. Furthermore, a potential role of mast cells in SARS-CoV-2-induced dysfunction of the capillary-alveolar interface adds to the growing understanding of mast cells in viral infections. The interaction between mast cells and microglial cells in the brain further highlights their significance in neuroinflammation. This review highlights the significant role of mast cells as the interface that acts as sensor and early responder through interactions with cells in systemic organs and the nervous system.
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Affiliation(s)
- Kottarappat N. Dileepan
- Division of Allergy, Clinical Immunology and Rheumatology, Department of Medicine, The University of Kansas Medical Center, Kansas City, KS, United States
| | - Vineesh V. Raveendran
- Division of Allergy, Clinical Immunology and Rheumatology, Department of Medicine, The University of Kansas Medical Center, Kansas City, KS, United States
| | - Rishi Sharma
- Department of Medicine, School of Medicine, University of Missouri, Kansas City, MO, United States
| | - Harita Abraham
- Division of Allergy, Clinical Immunology and Rheumatology, Department of Medicine, The University of Kansas Medical Center, Kansas City, KS, United States
| | - Rajat Barua
- Cardiology Section, Kansas City Veterans Affairs Medical Center, Kansas City, MO, United States
| | - Vikas Singh
- Neurology Section, Kansas City Veterans Affairs Medical Center, Kansas City, MO, United States
| | - Ram Sharma
- Research and Development Service, Kansas City Veterans Affairs Medical Center, Kansas City, MO, United States
| | - Mukut Sharma
- Research and Development Service, Kansas City Veterans Affairs Medical Center, Kansas City, MO, United States
- Midwest Veterans’ Biomedical Research Foundation (MVBRF), Kansas City VA Medical Center, Kansas, MO, United States
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14
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Song X, Zhang L, Du X, Zheng Y, Jia T, Zhou T, Che D, Geng S. Neuroblast Differentiation-Associated Protein Derived Polypeptides: AHNAK(5758-5775) Induces Inflammation by Activating Mast Cells via ST2. Immunol Invest 2023; 52:178-193. [PMID: 36511894 DOI: 10.1080/08820139.2022.2151368] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Psoriasis is a chronic inflammatory skin disease. Mast cells are significantly increased and activated in psoriatic lesions and are involved in psoriatic inflammation. Some endogenous substances can interact with the surface receptors of mast cells and initiate the release of downstream cytokines that participate in inflammatory reactions. Neuroblast differentiation-associated protein (AHNAK) is mainly expressed in the skin, esophagus, kidney, and other organs and participates in various biological processes in the human body. AHNAK and its derived peptides have been reported to be involved in the activation of mast cells and other immune processes. This study aimed to investigate whether AHNAK (5758-5775), a neuroblast differentiation-associated protein-derived polypeptide, could be considered a new endogenous substance in psoriasis patients, which activates mast cells and induces the skin inflammatory response contributing to psoriasis. Wild-type mice were treated with AHNAK(5758-5775) to observe the infiltration of inflammatory cells in the skin and cytokine release in vivo. The release of inflammatory mediators by mouse primary mast cells and the laboratory of allergic disease 2 (LAD2) human mast cells was measured in vitro. Molecular docking analysis, molecular dynamics simulation, and siRNA transfection were used to identify the receptor of AHNAK(5758-5775). AHNAK(5758-5775) could cause skin inflammation and cytokine release in wild-type mice and activated mast cells in vitro. Moreover, suppression of tumorigenicity 2 (ST2) might be a key receptor mediating AHNAK(5758-5775)'s effect on mast cells and cytokine release. We propose a novel polypeptide, AHNAK(5758-5775), which induces an inflammatory reaction and participates in the occurrence and development of psoriasis by activating mast cells.
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Affiliation(s)
- Xiangjin Song
- Department of Dermatology, Northwest Hospital, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Lei Zhang
- School of Pharmacy, Xi'an Jiaotong University, Xi'an, China
| | - Xueshan Du
- Department of Dermatology, Northwest Hospital, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.,Center for Dermatology Disease, Precision Medical Institute, Xi'an, China
| | - Yi Zheng
- Department of Dermatology, Northwest Hospital, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.,Center for Dermatology Disease, Precision Medical Institute, Xi'an, China
| | - Tao Jia
- Department of Dermatology, Northwest Hospital, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Tong Zhou
- Department of Dermatology, Northwest Hospital, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Delu Che
- Department of Dermatology, Northwest Hospital, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.,Center for Dermatology Disease, Precision Medical Institute, Xi'an, China
| | - Songmei Geng
- Department of Dermatology, Northwest Hospital, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.,Center for Dermatology Disease, Precision Medical Institute, Xi'an, China
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15
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Chen Y, Griffiths CEM, Bulfone-Paus S. Exploring Mast Cell-CD8 T Cell Interactions in Inflammatory Skin Diseases. Int J Mol Sci 2023; 24:1564. [PMID: 36675078 PMCID: PMC9861959 DOI: 10.3390/ijms24021564] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Revised: 01/09/2023] [Accepted: 01/11/2023] [Indexed: 01/15/2023] Open
Abstract
The skin is exposed to environmental challenges and contains skin-resident immune cells, including mast cells (MCs) and CD8 T cells that act as sentinels for pathogens and environmental antigens. Human skin MCs and their mediators participate in the maintenance of tissue homeostasis and regulate the recruitment and activity of immune cells involved in the pathogenesis of skin diseases. The cutaneous CD8 T cell compartment is comprised of long-persisting resident memory T cells (TRM) and migratory or recirculating cells; both populations provide durable site immune surveillance. Several lines of evidence indicate that MC-derived products, such as CCL5 and TNF-α, modulate the migration and function of CD8 T cells. Conversely, activated CD8 T cells induce the upregulation of MC costimulatory molecules. Moreover, the close apposition of MCs and CD8 T cells has been recently identified in the skin of several dermatoses, such as alopecia areata. This review outlines the current knowledge about bidirectional interactions between human MCs and CD8 T cells, analyses the alteration of their communication in the context of three common skin disorders in which these cells have been found altered in number or function-psoriasis, atopic dermatitis, and vitiligo-and discusses the current unanswered questions.
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Affiliation(s)
| | | | - Silvia Bulfone-Paus
- Lydia Becker Institute of Immunology and Inflammation, Dermatology Research Centre, NIHR Manchester Biomedical Research Centre, University of Manchester, Manchester M13 9PL, UK
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16
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Sericin-Based Poly(Vinyl) Alcohol Relieves Plaque and Epidermal Lesions in Psoriasis; a Chance for Dressing Development in a Specific Area. Int J Mol Sci 2022; 24:ijms24010145. [PMID: 36613589 PMCID: PMC9820396 DOI: 10.3390/ijms24010145] [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: 10/24/2022] [Revised: 12/16/2022] [Accepted: 12/16/2022] [Indexed: 12/24/2022] Open
Abstract
The noncontagious immune-mediated skin disease known as psoriasis is regarded as a chronic skin condition with a 0.09-11.4% global prevalence. The main obstacle to the eradication of the disease continues to be insufficient treatment options. Sericin, a natural biopolymer from Bombyx mori cocoons, can improve skin conditions via its immunomodulatory effect. Many external therapeutic methods are currently used to treat psoriasis, but sericin-based hydrogel is not yet used to treat plaques of eczema. Through the use of an imiquimod rat model, this study sought to identify the physical and chemical characteristics of a silk sericin-based poly(vinyl) alcohol (SS/PVA) hydrogel and assess both its therapeutic and toxic effects on psoriasis. The cytokines, chemokines, and genes involved in the pathogenesis of psoriasis were investigated, focusing on the immuno-pathological relationships. We discovered that the SS/PVA had a stable fabrication and proper release. Additionally, the anti-inflammatory, antioxidant, and anti-apoptotic properties of SS/PVA reduced the severity of psoriasis in both gross and microscopic skin lesions. This was demonstrated by a decrease in the epidermal histopathology score, upregulation of nuclear factor erythroid 2-related factor 2 and interleukin (IL)-10, and a decrease in the expression of tumor necrosis factor (TNF)-α and IL-20. Moreover, the genes S100a7a and S100a14 were downregulated. Additionally, in rats given the SS/PVA treatment, blood urea nitrogen, creatinine, and serum glutamic oxaloacetic transaminase levels were within normal limits. Our findings indicate that SS/PVA is safe and may be potentiated to treat psoriasis in a variety of forms and locations of plaque because of its physical, chemical, and biological characteristics.
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17
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Kim HS, Noh G. Immunotherapy using Histobulin™ in psoriasis: A case report. Clin Case Rep 2022; 10:e05831. [PMID: 35592052 PMCID: PMC9097755 DOI: 10.1002/ccr3.5831] [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: 01/06/2022] [Revised: 03/23/2022] [Accepted: 04/13/2022] [Indexed: 11/13/2022] Open
Abstract
There is no cure for psoriasis. A psoriasis patient was treated with Histobulin™. The patient's clinical symptoms and signs disappeared after the eighth injection and did not recur for more than 18 months. Histobulin™ was effective in the treatment of psoriasis and is suggested as a curative therapeutic for psoriasis. There is no cure for psoriasis, and early treatment is recommended to improve skin manifestations and systemic inflammation, which can lead to comorbidities in various organs. Histobulin™ was effective and induced remission in a psoriasis patient.
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Affiliation(s)
- Hyuk Soon Kim
- Department of Biomedical Sciences College of Natural Science and Department of Health Sciences The Graduate School of Dong‐A University Busan Korea
| | - Geunwoong Noh
- Allergy and Clinical Immunology Center Cheju Halla General Hospital Jeju‐si Korea
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18
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Li L, Liu X, Ge W, Chen C, Huang Y, Jin Z, Zhan M, Duan X, Liu X, Kong Y, Jiang J, Li X, Zeng X, Li F, Xu S, Li M, Chen H. CB2R Deficiency Exacerbates Imiquimod-Induced Psoriasiform Dermatitis and Itch Through the Neuro-Immune Pathway. Front Pharmacol 2022; 13:790712. [PMID: 35173615 PMCID: PMC8841964 DOI: 10.3389/fphar.2022.790712] [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: 10/07/2021] [Accepted: 01/05/2022] [Indexed: 12/02/2022] Open
Abstract
Background: Cannabinoid receptor 2 (CB2R) is a potential target for anti-inflammatory and pain therapeutics given its significant immunomodulatory and analgesic effects. However, the role of CB2R in imiquimod (IMQ)-induced psoriasiform dermatitis (PsD) and itch is poorly understood. Objective: To investigate the function and mechanism of CB2R in PsD and itch in mice. Methods: Following daily treatment with topical IMQ cream for 5-7 consecutive days in C56BL/6 wild-type (WT) and CB2R gene knockout (KO) mice, we assessed the Psoriasis Area and Severity Index (PASI) scores and the scratch bouts every day, and hematoxylin and eosin (H&E) staining, toluidine blue staining were used to observe the histological changes. mRNA levels were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). Protein levels were detected by western blotting (WB), immunohistochemistry (IHC), immunofluorescence (IF) and cytometric bead array (CBA). Flow cytometry (FCM) was used to examine the proportion of Th17/Treg cells. Results: We found that CB2R expression levels were increased in mice with psoriasis. Compared with WT mice, CB2R deficiency exacerbated IMQ-induced PsD and scratching bouts and upregulated the expression of proinflammatory cytokines by increasing the infiltration of CD4+ T cells and the Th17/Treg ratio. Obvious proliferation and prolongation of nerve fibers and high expression of nerve growth factor (NGF) were observed in PsD and CB2R KO mice. Pretreatment with the CB2R agonist, JWH-133 significantly reversed inflammation and scratching bouts. CB2R didn't participate in the induction of itch in psoriasis by regulating the expression of IL-31, thymic stromal lymphopoietin (TSLP) and mast cells in mouse skins. Conclusion: Our results demonstrate that CB2R plays a pivotal role in the pathophysiology of psoriasis, providing a new potential target for anti-inflammatory and antipruritic drugs.
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Affiliation(s)
- Li Li
- Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xin Liu
- Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Wenqiang Ge
- Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Chao Chen
- Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yuqiong Huang
- Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zilin Jin
- Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Muouyang Zhan
- Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xiaoru Duan
- Department of Rheumatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xinxin Liu
- Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yi Kong
- Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jian Jiang
- Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xuemei Li
- Department of Dermatology, Union Shenzhen Hospital, Huazhong University of Science and Technology, Shenzhen, China
| | - Xin Zeng
- Department of Dermatology, Union Shenzhen Hospital, Huazhong University of Science and Technology, Shenzhen, China
| | - Fei Li
- Department of Dermatology, Union Shenzhen Hospital, Huazhong University of Science and Technology, Shenzhen, China
| | - Shibin Xu
- Department of Dermatology, Union Shenzhen Hospital, Huazhong University of Science and Technology, Shenzhen, China
| | - Man Li
- Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Hongxiang Chen
- Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.,Department of Dermatology, Union Shenzhen Hospital, Huazhong University of Science and Technology, Shenzhen, China.,Department of Dermatology, The 6th Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, China
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19
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The Brain-Skin Axis in Psoriasis-Psychological, Psychiatric, Hormonal, and Dermatological Aspects. Int J Mol Sci 2022; 23:ijms23020669. [PMID: 35054853 PMCID: PMC8776235 DOI: 10.3390/ijms23020669] [Citation(s) in RCA: 45] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2021] [Revised: 01/05/2022] [Accepted: 01/06/2022] [Indexed: 02/04/2023] Open
Abstract
Psoriasis is a chronic inflammatory skin disease with systemic manifestation, in which psychological factors play an important role. The etiology of psoriasis is complex and multifactorial, including genetic background and environmental factors such as emotional or physical stress. Psychological stress may also play a role in exacerbation of psoriasis, by dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis, sympathetic–adrenal–medullary axis, peripheral nervous system, and immune system. Skin cells also express various neuropeptides and hormones in response to stress, including the fully functional analog of the HPA axis. The deterioration of psoriatic lesions is accompanied by increased production of inflammatory mediators, which could contribute to the imbalance of neurotransmitters and the development of symptoms of depression and anxiety. Therefore, deregulation of the crosstalk between endocrine, paracrine, and autocrine stress signaling pathways contributes to clinical manifestations of psoriasis, which requires multidisciplinary approaches.
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20
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Pejler G, Alanazi S, Grujic M, Adler J, Olsson AK, Sommerhoff CP, Rabelo Melo F. Mast Cell Tryptase Potentiates Neutrophil Extracellular Trap Formation. J Innate Immun 2021; 14:433-446. [PMID: 34937018 PMCID: PMC9485958 DOI: 10.1159/000520972] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2021] [Accepted: 10/26/2021] [Indexed: 11/26/2022] Open
Abstract
Previous research has indicated an intimate functional communication between mast cells (MCs) and neutrophils during inflammatory conditions, but the nature of such communication is not fully understood. Activated neutrophils are known to release DNA-containing extracellular traps (neutrophil extracellular traps [NETs]) and, based on the known ability of tryptase to interact with negatively charged polymers, we here hypothesized that tryptase might interact with NET-contained DNA and thereby regulate NET formation. In support of this, we showed that tryptase markedly enhances NET formation in phorbol myristate acetate-activated human neutrophils. Moreover, tryptase was found to bind vividly to the NETs, to cause proteolysis of core histones and to cause a reduction in the levels of citrullinated histone-3. Secretome analysis revealed that tryptase caused increased release of numerous neutrophil granule compounds, including gelatinase, lactoferrin, and myeloperoxidase. We also show that DNA can induce the tetrameric, active organization of tryptase, suggesting that NET-contained DNA can maintain tryptase activity in the extracellular milieu. In line with such a scenario, DNA-stabilized tryptase was shown to efficiently degrade numerous pro-inflammatory compounds. Finally, we showed that tryptase is associated with NET formation in vivo in a melanoma setting and that NET formation in vivo is attenuated in mice lacking tryptase expression. Altogether, these findings reveal that NET formation can be regulated by MC tryptase, thus introducing a novel mechanism of communication between MCs and neutrophils.
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Affiliation(s)
- Gunnar Pejler
- Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden
- *Gunnar Pejler,
| | - Sultan Alanazi
- Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden
| | - Mirjana Grujic
- Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden
| | - Jeremy Adler
- Department of Immunology, Genetics and Pathology − BioVis, Uppsala University, Uppsala, Sweden
| | - Anna-Karin Olsson
- Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden
| | | | - Fabio Rabelo Melo
- Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden
- **Fabio Rabelo Melo,
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21
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Does the lifestyle of patients with psoriasis affect their illness? POSTEP HIG MED DOSW 2021. [DOI: 10.2478/ahem-2021-0033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Abstract
Psoriasis is one of the most common chronic, incurable inflammatory skin diseases, affecting 2–4% of the general population. Etiopathogenesis of this disease remains unclear. It is widely considered to be a multifactorial disorder caused by the interaction between inherited susceptibility alleles and environmental risk factors, such as lifestyle, diet, stimulants, foci of inflammation, and psychological factors. The widespread prevalence of psoriasis is a very significant health and socioeconomic problem. Treatment of psoriasis is based on relieving the acute symptoms of the disease. Despite the implementation of many therapeutic options, including biological treatment, effectiveness of these options is not always sufficient, or in some patients it is not satisfactory. In order to properly control the symptoms of the disease, the patient should be told that the therapeutic effect is achieved not only by pharmacotherapy but also by introducing appropriate healthy habits in everyday life. This article discusses the importance of patient-controlled factors that affect the severity of psoriasis. Theimportance of regular exercise, smoking avoidance, and reduced alcohol consumption is explained, as well as the importance for psoriasis treatment of psychotherapy and spa therapy. Understanding the essence of these factors in the treatment of psoriasis is important in achieving satisfactory therapeutic effects.
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22
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Kallionpää RA, Ahramo K, Martikkala E, Fazeli E, Haapaniemi P, Rokka A, Leivo I, Harvima IT, Peltonen J, Peltonen S. Mast Cells in Human Cutaneous Neurofibromas: Density, Subtypes, and Association with Clinical Features in Neurofibromatosis 1. Dermatology 2021; 238:329-339. [PMID: 34237737 DOI: 10.1159/000517011] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2021] [Accepted: 04/24/2021] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND Cutaneous neurofibromas (cNFs) are hallmarks of neurofibromatosis 1 (NF1) and cause the main disease burden in adults with NF1. Mast cells are a known component of cNFs. However, no comprehensive characterization of mast cells in cNFs is available, and their contributions to cNF growth and symptoms such as itch are not known. METHODS We collected 60 cNFs from ten individuals with NF1, studied their mast cell proteinase content, and compared the mast cell numbers to selected clinical features of the tumors and patients. The tumors were immunolabeled for the mast cell markers CD117, tryptase, and chymase, and the percentage of immunopositive cells was determined using computer-assisted methods. RESULTS The median proportions of positive cells were 5.5% (range 0.1-14.4) for CD117, 4.0% (1.2-7.0) for tryptase, and 5.0% (1.1-15.9) for chymase. The median densities of cells immunopositive for CD117, tryptase, and chymase were 280, 243, and 250 cells/mm2, respectively. Small tumors, growing tumors, and tumors from patients below the median age of 33 years displayed a high proportion of mast cells. Cells expressing both tryptase and chymase were the predominant mast cell type in cNFs, followed by cells expressing chymase only. CONCLUSION The results highlight the abundance of mast cells in cNFs and that their number and subtypes clearly differ from those previously reported in unaffected skin.
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Affiliation(s)
| | - Kaisa Ahramo
- Institute of Biomedicine, University of Turku, Turku, Finland
| | - Eija Martikkala
- Institute of Biomedicine, University of Turku, Turku, Finland
| | - Elnaz Fazeli
- Institute of Biomedicine, University of Turku, Turku, Finland
| | - Pekka Haapaniemi
- Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland
| | - Anne Rokka
- Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland
| | - Ilmo Leivo
- Institute of Biomedicine, University of Turku, Turku, Finland.,Department of Pathology, Turku University Hospital, Turku, Finland
| | - Ilkka T Harvima
- Department of Dermatology, Kuopio University Hospital and University of Eastern Finland, Kuopio, Finland
| | - Juha Peltonen
- Institute of Biomedicine, University of Turku, Turku, Finland
| | - Sirkku Peltonen
- Department of Dermatology and Venereology, University of Turku, Turku, Finland.,Department of Dermatology, Turku University Hospital, Turku, Finland.,Department of Dermatology and Venereology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.,Department of Dermatology and Venereology, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden
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Yadav M, Sardana I, Sharma A, Sharma N, Nagpal K, Malik P. Emerging Pathophysiological Targets of Psoriasis for Future Therapeutic Strategies. Infect Disord Drug Targets 2021; 20:409-422. [PMID: 31288731 DOI: 10.2174/1871526519666190617162701] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2019] [Revised: 04/04/2019] [Accepted: 04/13/2019] [Indexed: 12/28/2022]
Abstract
Psoriasis is a chronic autoimmune skin disorder which involves complex interactions between genes, keratinocytes, T-cells and inflammatory cells. It affects 2-3% population worldwide. Molecular biology and cellular immunology of psoriasis, when linked with biotechnology and genetic studies can help researchers to understand the pathophysiology of psoriasis. T-cells activation, keratinocyte hyperproliferation, and angiogenesis are the core mechanisms entailed in the development of psoriasis lesion. Investigators are trying to overcome the challenges of complex pathophysiology pathways involved in this disorder. The different possible hypotheses for its pathophysiology such as growth factors, enzymes, inflammation, and genetic factors mediated pathophysiology have been described in the present review paper in detail. Clinically available drugs only control the symptoms of psoriasis but are not effective for the treatment of the disorder completely and are also associated with some side effects such as itching, renal disorders, hematologic, nonmelanoma skin cancer, pulmonary, gastrointestinal toxicity, etc. This paper made an effort to understand the pathophysiological targets, discuss the research done so far and the treatments available for the effective management of psoriasis.
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Affiliation(s)
- Monu Yadav
- Department of Pharmaceutical Sciences, Chaudhary Bansi Lal University, Bhiwani-127021, Haryana, India
| | - Ishu Sardana
- Department of Pharmaceutical Sciences, Chaudhary Bansi Lal University, Bhiwani-127021, Haryana, India
| | - Amarjeet Sharma
- Department of Pharmaceutical Sciences, Chaudhary Bansi Lal University, Bhiwani-127021, Haryana, India
| | - Nidhi Sharma
- Shri Baba Mastnath Institute of Pharmaceutical Science and Research, Rohtak -124001, Haryana, India
| | - Kalpana Nagpal
- Amity Institute of Pharmacy, Amity University Noida- 201313, Uttar Pradesh, India
| | - Paramjeet Malik
- Department of Pharmaceutical Sciences, Chaudhary Bansi Lal University, Bhiwani-127021, Haryana, India
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24
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Voss M, Kotrba J, Gaffal E, Katsoulis-Dimitriou K, Dudeck A. Mast Cells in the Skin: Defenders of Integrity or Offenders in Inflammation? Int J Mol Sci 2021; 22:ijms22094589. [PMID: 33925601 PMCID: PMC8123885 DOI: 10.3390/ijms22094589] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 04/23/2021] [Accepted: 04/25/2021] [Indexed: 12/13/2022] Open
Abstract
Mast cells (MCs) are best-known as key effector cells of immediate-type allergic reactions that may even culminate in life-threatening anaphylactic shock syndromes. However, strategically positioned at the host–environment interfaces and equipped with a plethora of receptors, MCs also play an important role in the first-line defense against pathogens. Their main characteristic, the huge amount of preformed proinflammatory mediators embedded in secretory granules, allows for a rapid response and initiation of further immune effector cell recruitment. The same mechanism, however, may account for detrimental overshooting responses. MCs are not only detrimental in MC-driven diseases but also responsible for disease exacerbation in other inflammatory disorders. Focusing on the skin as the largest immune organ, we herein review both beneficial and detrimental functions of skin MCs, from skin barrier integrity via host defense mechanisms to MC-driven inflammatory skin disorders. Moreover, we emphasize the importance of IgE-independent pathways of MC activation and their role in sustained chronic skin inflammation and disease exacerbation.
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Affiliation(s)
- Martin Voss
- Medical Faculty, Institute for Molecular and Clinical Immunology, Otto-Von-Guericke-University Magdeburg, 39120 Magdeburg, Germany; (M.V.); (J.K.); (K.K.-D.)
| | - Johanna Kotrba
- Medical Faculty, Institute for Molecular and Clinical Immunology, Otto-Von-Guericke-University Magdeburg, 39120 Magdeburg, Germany; (M.V.); (J.K.); (K.K.-D.)
| | - Evelyn Gaffal
- Laboratory for Experimental Dermatology, Department of Dermatology, University Hospital Magdeburg, 39120 Magdeburg, Germany;
| | - Konstantinos Katsoulis-Dimitriou
- Medical Faculty, Institute for Molecular and Clinical Immunology, Otto-Von-Guericke-University Magdeburg, 39120 Magdeburg, Germany; (M.V.); (J.K.); (K.K.-D.)
| | - Anne Dudeck
- Medical Faculty, Institute for Molecular and Clinical Immunology, Otto-Von-Guericke-University Magdeburg, 39120 Magdeburg, Germany; (M.V.); (J.K.); (K.K.-D.)
- Health Campus Immunology, Infectiology and Inflammation, Otto-Von-Guericke-University Magdeburg, 39120 Magdeburg, Germany
- Correspondence:
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25
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Serhan N, Cenac N, Basso L, Gaudenzio N. Mas-related G protein-coupled receptors (Mrgprs) - Key regulators of neuroimmune interactions. Neurosci Lett 2021; 749:135724. [PMID: 33600909 DOI: 10.1016/j.neulet.2021.135724] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2020] [Revised: 02/03/2021] [Accepted: 02/05/2021] [Indexed: 02/06/2023]
Abstract
Interplay between physiological systems in the body plays a prominent role in health and disease. At the cellular level, such interplay is orchestrated through the binding of specific ligands to their receptors expressed on cell surface. G protein-coupled receptors (GPCR) are seven-transmembrane domain receptors that initiate various cellular responses and regulate homeostasis. In this review, we focus on particular GPCRs named Mas-related G protein-coupled receptors (Mrgprs) mainly expressed by sensory neurons and specialized immune cells. We describe the different subfamilies of Mrgprs and their specific ligands, as well as recent advances in the field that illustrate the role played by these receptors in neuro-immune biological processes, including itch, pain and inflammation in diverse organs.
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Affiliation(s)
- Nadine Serhan
- Toulouse Institute for Infectious and Inflammatory Diseases, INSERM UMR1291, CNRS UMR5051, University of Toulouse III, Toulouse, France
| | - Nicolas Cenac
- IRSD, Université de Toulouse, INSERM, INRA, INP-ENVT, Université de Toulouse 3 Paul Sabatier, Toulouse, France
| | - Lilian Basso
- Toulouse Institute for Infectious and Inflammatory Diseases, INSERM UMR1291, CNRS UMR5051, University of Toulouse III, Toulouse, France.
| | - Nicolas Gaudenzio
- Toulouse Institute for Infectious and Inflammatory Diseases, INSERM UMR1291, CNRS UMR5051, University of Toulouse III, Toulouse, France.
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26
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Illuminating the Role of Vitamin A in Skin Innate Immunity and the Skin Microbiome: A Narrative Review. Nutrients 2021; 13:nu13020302. [PMID: 33494277 PMCID: PMC7909803 DOI: 10.3390/nu13020302] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2020] [Revised: 01/18/2021] [Accepted: 01/19/2021] [Indexed: 12/11/2022] Open
Abstract
Vitamin A is a fat-soluble vitamin that plays an important role in skin immunity. Deficiencies in Vitamin A have been linked to impaired immune response and increased susceptibility to skin infections and inflammatory skin disease. This narrative review summarizes recent primary evidence that elucidates the role of vitamin A and its derivatives on innate immune regulators through mechanisms that promote skin immunity and sustain the skin microbiome.
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27
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Jaworecka K, Muda-Urban J, Rzepko M, Reich A. Molecular Aspects of Pruritus Pathogenesis in Psoriasis. Int J Mol Sci 2021; 22:ijms22020858. [PMID: 33467067 PMCID: PMC7830783 DOI: 10.3390/ijms22020858] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2020] [Revised: 01/11/2021] [Accepted: 01/13/2021] [Indexed: 12/23/2022] Open
Abstract
Psoriasis is a chronic, systemic inflammatory disease with a genetic background that involves almost 3% of the general population worldwide. Approximately, 70–90% of patients with psoriasis suffer from pruritus, an unpleasant sensation that provokes a desire to scratch. Despite the enormous progress in understanding the mechanisms that cause psoriasis, the pathogenesis of psoriasis-related pruritus still remains unclear. In order to improve patients’ quality of life, development of more effective and safer antipruritic therapies is necessary. In turn to make it possible, better understanding of complexed and multifactorial pathogenesis of this symptom is needed. In this article we have systematized the current knowledge about pruritus origin in psoriasis.
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Affiliation(s)
- Kamila Jaworecka
- Department of Dermatology, Institute of Medical Sciences, Medical College of Rzeszow University, PL-35-055 Rzeszow, Poland; (K.J.); (J.M.-U.)
| | - Joanna Muda-Urban
- Department of Dermatology, Institute of Medical Sciences, Medical College of Rzeszow University, PL-35-055 Rzeszow, Poland; (K.J.); (J.M.-U.)
| | - Marian Rzepko
- Institute of Physical Culture Sciences, Medical College of Rzeszow University, PL-35-055 Rzeszow, Poland;
| | - Adam Reich
- Department of Dermatology, Institute of Medical Sciences, Medical College of Rzeszow University, PL-35-055 Rzeszow, Poland; (K.J.); (J.M.-U.)
- Correspondence: ; Tel.: +48-605076722
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28
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Rawat K, Syeda S, Shrivastava A. Neutrophil-derived granule cargoes: paving the way for tumor growth and progression. Cancer Metastasis Rev 2021; 40:221-244. [PMID: 33438104 PMCID: PMC7802614 DOI: 10.1007/s10555-020-09951-1] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2020] [Accepted: 12/22/2020] [Indexed: 01/31/2023]
Abstract
Neutrophils are the key cells of our innate immune system mediating host defense via a range of effector functions including phagocytosis, degranulation, and NETosis. For this, they employ an arsenal of anti-microbial cargoes packed in their readily mobilizable granule subsets. Notably, the release of granule content is tightly regulated; however, under certain circumstances, their unregulated release can aggravate tissue damage and could be detrimental to the host. Several constituents of neutrophil granules have also been associated with various inflammatory diseases including cancer. In cancer setting, their excessive release may modulate tissue microenvironment which ultimately leads the way for tumor initiation, growth and metastasis. Neutrophils actively infiltrate within tumor tissues, wherein they show diverse phenotypic and functional heterogeneity. While most studies are focused at understanding the phenotypic heterogeneity of neutrophils, their functional heterogeneity, much of which is likely orchestrated by their granule cargoes, is beginning to emerge. Therefore, a better understanding of neutrophil granules and their cargoes will not only shed light on their diverse role in cancer but will also reveal them as novel therapeutic targets. This review provides an overview on existing knowledge of neutrophil granules and detailed insight into the pathological relevance of their cargoes in cancer. In addition, we also discuss the therapeutic approach for targeting neutrophils or their microenvironment in disease setting that will pave the way forward for future research.
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Affiliation(s)
- Kavita Rawat
- grid.8195.50000 0001 2109 4999Department of Zoology, University of Delhi, Delhi, 110007 India
| | - Saima Syeda
- grid.8195.50000 0001 2109 4999Department of Zoology, University of Delhi, Delhi, 110007 India
| | - Anju Shrivastava
- grid.8195.50000 0001 2109 4999Department of Zoology, University of Delhi, Delhi, 110007 India
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29
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Molecular and Cellular Mechanisms of Itch in Psoriasis. Int J Mol Sci 2020; 21:ijms21218406. [PMID: 33182442 PMCID: PMC7664892 DOI: 10.3390/ijms21218406] [Citation(s) in RCA: 53] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2020] [Revised: 11/05/2020] [Accepted: 11/06/2020] [Indexed: 02/06/2023] Open
Abstract
Itch (or pruritus) was not previously recognized as a serious symptom of psoriasis. However, approximately 60-90% of psoriatic patients with pruritus have stated that it deteriorates their quality of life. Since conventional antipruritic therapies, such as antihistamines, only exert limited effects, the establishment of a treatment option for itch in psoriasis is urgently needed. Although a definitive drug is not currently available, various itch mediators are known to be involved in pruritus in psoriasis. In this review, we describe the clinical features of pruritus in psoriasis, classify a wide range of itch mediators into categories, such as the nervous, immune, endocrine, and vascular systems, and discuss the mechanisms by which these mediators induce or aggravate itch in the pathophysiology of psoriasis.
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30
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Damiani G, Kridin K, Pacifico A, Malagoli P, Pigatto PDM, Finelli R, Taccone FS, Peluso L, Conic RRZ, Bragazzi NL, Fiore M. Antihistamines-refractory chronic pruritus in psoriatic patients undergoing biologics: aprepitant vs antihistamine double dosage, a real-world data. J DERMATOL TREAT 2020; 33:1554-1557. [PMID: 33084462 DOI: 10.1080/09546634.2020.1840502] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
BACKGROUND Psoriasis-related pruritus (PRP) in patients under systemic treatment is challenging. The risk to switch anti-psoriatic drugs and to lose response to previous therapy is high, thus dermatologists prefer to add an anti-pruritic agent. OBJECTIVES To evaluate the effect of anti-histamines and aprepitant in treating PPR of psoriatic patients undergoing systemic anti-psoriatic therapies. METHODS A pilot observational open-label study was performed on responsive psoriatic patients with PPR under treatment. Initial therapy included oral rupatadine (10 mg/day for 30 days). In case of the Epworth Sleepiness Scale (ESS) was above 14, patients were switched to aprepitant (80 mg/day for 7 days), otherwise, rupatadine dosage was increased (20 mg/day for 7 days). Clinical evaluation was performed at the baseline (T0) and after 7 days (T7). RESULTS We enrolled 40 patients with PPR, 20 in each group. Age, gender, Psoriatic arthritis (PsA) and the itch - VAS, were matched. At T7, aprepitant displayed higher improvements than rupatadine (itch - VAS = 4 [3-5] vs 8.5 [8-9], p < .01, DLQI = 14 [13-16] vs. 18 [16-21], p < .01 and ESS = 5 [4-7] vs 15 [14-16], p < .01). Doubling the rupatadine dosage from 10 mg to 20 mg/day only slightly improve itch (itch - VAS = 9 [8-10] vs 9 [8-9], p = .03), conversely no modifications in the quality of life (DLQI = 18 [17-20] vs 18 [17-21], p = .73) and increased sleepiness (ESS = 10 [9-11] vs 15 [14-16], p < .01). CONCLUSIONS Aprepitant may be a valid alternative in PPR patients with ESS >14 under antihistamines.
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Affiliation(s)
- Giovanni Damiani
- Department of Clinical Dermatology, IRCCS Istituto Ortopedico Galeazzi, Milan, Italy.,Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy
| | | | - Alessia Pacifico
- Clinical Dermatology Department, IRCCS S. Gallicano Dermatological Institute, Rome, Italy
| | | | - Paolo D M Pigatto
- Department of Clinical Dermatology, IRCCS Istituto Ortopedico Galeazzi, Milan, Italy.,Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy
| | | | - Fabio S Taccone
- Department of Intensive Care, Erasme Hospital, Université libre de Bruxelles, Brussel, Belgium
| | - Lorenzo Peluso
- Department of Intensive Care, Erasme Hospital, Université libre de Bruxelles, Brussel, Belgium
| | | | - Nicola L Bragazzi
- Laboratory for Industrial and Applied Mathematics (LIAM), Department of Mathematics and Statistics, York University, Toronto, Canada
| | | | - Marco Fiore
- Young Dermatologists Italian Network, Bergamo, Italy.,Department of Women, Child and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy
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31
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Zhao J, Xie P, Galiano RD, Qi S, Mao R, Mustoe TA, Hong SJ. Imiquimod-induced skin inflammation is relieved by knockdown of sodium channel Na x. Exp Dermatol 2020; 28:576-584. [PMID: 30903711 DOI: 10.1111/exd.13917] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2018] [Revised: 02/22/2019] [Accepted: 02/28/2019] [Indexed: 12/30/2022]
Abstract
Nax is an atypical sodium channel that mediates inflammatory pathways in pathological conditions of the skin. In this study, we developed a skin inflammation model in the rabbit ear through application of imiquimod (IMQ). Knockdown of Nax using RNAi attenuated IMQ-induced skin inflammation, including skin erythema, scaling and papule formation. Histologic analysis showed that thickening and insufficient differentiation of the epidermis found in psoriasis-like skin were normalized by administration of Nax -RNAi. Excessive infiltration of inflammatory cells found in inflammatory lesions, such as mast cells, eosinophils, neutrophils, T cells and macrophages, was reduced by Nax -RNAi. Expression of S100A9, which is a downstream gene of Nax and a mediator of inflammation, was decreased by Nax -RNAi. Our results demonstrated that knockdown of Nax ameliorated IMQ-induced psoriasis-like skin inflammation in vivo. Thus, targeting of Nax may represent a potential therapeutic option for the treatment of psoriasis.
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Affiliation(s)
- Jingling Zhao
- Department of Burns, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.,Department of Surgery/Plastic Surgery Division, Laboratory for Tissue Repair and Regenerative Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illionis
| | - Ping Xie
- Department of Surgery/Plastic Surgery Division, Laboratory for Tissue Repair and Regenerative Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illionis
| | - Robert D Galiano
- Department of Surgery/Plastic Surgery Division, Laboratory for Tissue Repair and Regenerative Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illionis
| | - Shaohai Qi
- Department of Burns, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Renxiang Mao
- Department of Dermatology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Thomas A Mustoe
- Department of Surgery/Plastic Surgery Division, Laboratory for Tissue Repair and Regenerative Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illionis
| | - Seok Jong Hong
- Department of Surgery/Plastic Surgery Division, Laboratory for Tissue Repair and Regenerative Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illionis
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32
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Magen E, Chikovani T. Recurrent spontaneous clearance of psoriasis during exacerbations of concomitant chronic spontaneous urticaria. Clin Case Rep 2020; 8:1544-1546. [PMID: 32884792 PMCID: PMC7455433 DOI: 10.1002/ccr3.2930] [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: 01/11/2020] [Revised: 04/06/2020] [Accepted: 04/15/2020] [Indexed: 11/07/2022] Open
Abstract
In this case report, we describe a patient with a chronological relationship between exacerbations of chronic spontaneous urticaria and remissions of concomitant generalized plaque psoriasis.
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Affiliation(s)
- Eli Magen
- Allergy and Clinical Immunology UnitMedicine C DepartmentBarzilai Medical CenterBen Gurion University of NegevAshkelonIsrael
| | - Tinatin Chikovani
- Department of ImmunologyTbilisi State Medical UniversityTbilisiGeorgia
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33
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Wang X, Lai Q, Zheng B, Ye L, Wen S, Yan Y, Yang B, Man MQ. Prevalence and Severity of Dermatological Condition-Associated Skin Pain in the Chinese. J Pain Res 2020; 13:1201-1207. [PMID: 32581569 PMCID: PMC7266942 DOI: 10.2147/jpr.s245514] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND/AIM Although the characteristics of cutaneous sensory symptoms in the general population have been documented, dermatological condition-associated skin pain has not been characterized yet. In the present study, we aimed to characterize dermatological condition-associated skin pain in the Chinese. SUBJECTS AND METHODS A questionnaire was given to outpatients to identify self-proclaimed skin pain at our dermatology clinic. The severity of skin pain was assessed using pain scale 0-10. Prevalence and pain severity were compared between males and females. RESULTS A total of 2144 patients, including 1254 females and 890 males aged 13-94 years, were included in this study. The overall prevalence of skin pain was 9.93% in this cohort. The prevalence of skin pain varied greatly with dermatological conditions (p<0.0001). Moreover, a higher prevalence of skin pain was observed in males than in females (p<0.05). Among the dermatological conditions reported, higher skin pain scales were found in subjects with either glucocorticoid-induced dermatitis (4.20 ± 0.73) or herpes zoster (4.00 ± 0.29). While the overall pain scales were comparable between males and females (2.38 ± 0.13 versus 2.68 ± 0.13), pain scales in patients with eczematous dermatitis were higher in females than in males (p<0.05). Furthermore, pain scales correlated positively with age. However, pain scales did not differ between subjects with versus without a family history of cutaneous sensory symptoms. These results demonstrate that the prevalence and severity of dermatological condition-associated skin pain vary with dermatological conditions and gender in the Chinese. CONCLUSION Patients with some dermatological conditions may experience skin pain. Although the pain is moderate, it can negatively impact the quality of patients' lives. Alleviation of skin pain should be considered when treating patients with certain dermatological conditions.
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Affiliation(s)
- Xiaohua Wang
- Dermatology Hospital, Southern Medical University, Guangdong510095, People’s Republic of China
| | - Qingsong Lai
- Puning City Chronic Disease Prevention and Control Center, Guangdong515300, People’s Republic of China
| | - Baoqing Zheng
- Dermatology Hospital, Southern Medical University, Guangdong510095, People’s Republic of China
| | - Li Ye
- Dermatology Hospital, Southern Medical University, Guangdong510095, People’s Republic of China
| | - Si Wen
- Dermatology Hospital, Southern Medical University, Guangdong510095, People’s Republic of China
| | - Yunling Yan
- Dermatology Hospital, Southern Medical University, Guangdong510095, People’s Republic of China
| | - Bin Yang
- Dermatology Hospital, Southern Medical University, Guangdong510095, People’s Republic of China
| | - Mao-Qiang Man
- Dermatology Hospital, Southern Medical University, Guangdong510095, People’s Republic of China
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34
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Mueller SM, Navarini AA, Goldust M, Brandt O, Griffiths CEM, Kleyn CE. The short-term effect of levocetirizine on quality of life, stress, and depression in itchy psoriasis patients. Dermatol Ther 2019; 33:e13179. [PMID: 31769907 DOI: 10.1111/dth.13179] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2019] [Accepted: 11/23/2019] [Indexed: 12/01/2022]
Affiliation(s)
- Simon M Mueller
- Department of Dermatology, University Hospital Basel, Basel, Switzerland.,Dermatology Centre, The Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK
| | - Alexander A Navarini
- Department of Dermatology and Allergy, University Hospital of Basel, Basel, Switzerland
| | - Mohamad Goldust
- Department of Dermatology, University Hospital Basel, Basel, Switzerland.,Department of Dermatology, University of Rome G. Marconi, Rome, Italy.,Department of Dermatology, University Medical Center Mainz, Mainz, Germany
| | - Oliver Brandt
- Department of Dermatology, University Hospital Basel, Basel, Switzerland
| | - Christopher E M Griffiths
- Dermatology Centre, The Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK
| | - Christine E Kleyn
- Dermatology Centre, The Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK
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35
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Mueller SM, Navarini AA, Goldust M, Brandt O, Griffiths CEM, Kleyn CE. Levocetirizine for the treatment of itch in psoriasis patients: An open‐label pilot study in a real‐world setting. Dermatol Ther 2019; 33:e13166. [DOI: 10.1111/dth.13166] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2019] [Accepted: 11/10/2019] [Indexed: 12/01/2022]
Affiliation(s)
- Simon M. Mueller
- Department of DermatologyUniversity Hospital Basel Basel Switzerland
- Department of Dermatology & AllergyUniversity Hospital of Basel Basel Switzerland
| | | | - Mohamad Goldust
- Department of DermatologyUniversity Hospital Basel Basel Switzerland
- Department of DermatologyUniversity of Rome Guglielmo Marconi Rome Italy
- Department of DermatologyUniversity Medical Center Mainz Mainz Germany
| | - Oliver Brandt
- Department of DermatologyUniversity Hospital Basel Basel Switzerland
| | | | - Christine E. Kleyn
- Dermatology Centre, The Manchester Academic Health Science CentreThe University of Manchester Manchester UK
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36
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Possible Roles of IL-33 in the Innate-Adaptive Immune Crosstalk of Psoriasis Pathogenesis. Mediators Inflamm 2019; 2019:7158014. [PMID: 31736655 PMCID: PMC6815589 DOI: 10.1155/2019/7158014] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2019] [Accepted: 08/26/2019] [Indexed: 01/18/2023] Open
Abstract
Background IL-33 belongs to the IL-1 family, playing a role in several biologic processes as well as in the pathogenesis of different diseases, including skin pathologies. It acts as an alarmin, released by damaged cells. Binding to a ST2 receptor, it stimulates many immune cells such as ILC2 and Th2 cells. IL-33/ST2 axis seems to be involved in Th17 response. According to this, a review was performed to analyze if IL-33 even interplay in the onset of psoriasis, a Th1/Th17 inflammatory disease. Methods Data obtained from the included articles are study author name, publication date, group studied, clinical and biological variables, laboratory tests, and outcome of interest of the study. Results Data are obtained from the 19 studies identified, which assessed the association between IL-33 and psoriasis. Discussion It seems to promote the innate-adaptive immune crosstalk: it could induce mast cells and neutrophil response after being released by injured keratinocytes and after stimulation by some cytokines, in particular TNFα, INFγ, and IL-17A. In addition, it seems to be involved from the onset of disease to the development of comorbidities, as psoriatic arthritis. Conclusion The core of the future research on psoriasis could be to fully understand the role of this complex cytokine, in order also to find a new therapeutic approach.
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37
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Chiang CC, Cheng WJ, Korinek M, Lin CY, Hwang TL. Neutrophils in Psoriasis. Front Immunol 2019; 10:2376. [PMID: 31649677 PMCID: PMC6794444 DOI: 10.3389/fimmu.2019.02376] [Citation(s) in RCA: 173] [Impact Index Per Article: 28.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2019] [Accepted: 09/23/2019] [Indexed: 12/22/2022] Open
Abstract
Neutrophils are the most abundant innate immune cells. The pathogenic roles of neutrophils are related to chronic inflammation and autoimmune diseases. Psoriasis is a chronic systemic inflammatory disease affecting ~2–3% of the world population. The abundant presence of neutrophils in the psoriatic skin lesions serves as a typical histopathologic hallmark of psoriasis. Recent reports indicated that oxidative stress, granular components, and neutrophil extracellular traps from psoriatic neutrophils are related to the initial and maintenance phases of psoriasis. This review provides an overview on the recent (up to 2019) advances in understanding the role of neutrophils in the pathophysiology of psoriasis, including the effects of respiratory burst, degranulation, and neutrophil extracellular trap formation on psoriatic immunity and the clinical relationships.
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Affiliation(s)
- Chih-Chao Chiang
- Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.,Supervisor Board, Taoyuan Chinese Medicine Association, Taoyuan, Taiwan.,Puxin Fengze Chinese Medicine Clinic, Taoyuan, Taiwan
| | - Wei-Jen Cheng
- Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.,School of Traditional Chinese Medicine, Chang Gung University, Taoyuan, Taiwan.,Center for Traditional Chinese Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Michal Korinek
- Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Taoyuan, Taiwan.,Research Center for Chinese Herbal Medicine, Research Center for Food and Cosmetic Safety, and Graduate Institute of Health Industry Technology, Chang Gung University of Science and Technology, Taoyuan, Taiwan.,Department of Biotechnology, College of Life Science, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Cheng-Yu Lin
- Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Tsong-Long Hwang
- School of Traditional Chinese Medicine, Chang Gung University, Taoyuan, Taiwan.,Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Taoyuan, Taiwan.,Research Center for Chinese Herbal Medicine, Research Center for Food and Cosmetic Safety, and Graduate Institute of Health Industry Technology, Chang Gung University of Science and Technology, Taoyuan, Taiwan.,Chinese Herbal Medicine Research Team, Healthy Aging Research Center, Chang Gung University, Taoyuan, Taiwan.,Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.,Department of Chemical Engineering, Ming Chi University of Technology, New Taipei City, Taiwan
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38
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Siiskonen H, Harvima I. Mast Cells and Sensory Nerves Contribute to Neurogenic Inflammation and Pruritus in Chronic Skin Inflammation. Front Cell Neurosci 2019; 13:422. [PMID: 31619965 PMCID: PMC6759746 DOI: 10.3389/fncel.2019.00422] [Citation(s) in RCA: 101] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2018] [Accepted: 09/03/2019] [Indexed: 12/12/2022] Open
Abstract
The intimate interaction between mast cells and sensory nerves can be illustrated by the wheal and surrounding flare in an urticarial reaction in human skin. This reaction is typically associated with an intense itch at the reaction site. Upon activation, cutaneous mast cells release powerful mediators, such as histamine, tryptase, cytokines, and growth factors that can directly stimulate corresponding receptors on itch-mediating sensory nerves. These include, e.g., H1- and H4-receptors, protease-activated receptor-2, IL-31 receptor, and the high-affinity receptor of nerve growth factor (TrkA). On the other hand, sensory nerves can release neuropeptides, including substance P and vasoactive intestinal peptide, that are able to stimulate mast cells to release mediators leading to potentiation of the reciprocal interaction, inflammation, and itch. Even though mast cells are well recognized for their role in allergic skin whealing and urticaria, increasing evidence supports the reciprocal function between mast cells and sensory nerves in neurogenic inflammation in chronic skin diseases, such as psoriasis and atopic dermatitis, which are often characterized by distressing itch, and exacerbated by psychological stress. Increased morphological contacts between mast cells and sensory nerves in the lesional skin in psoriasis and atopic dermatitis as well as experimental models in mice and rats support the essential role for mast cell-sensory nerve communication in consequent pruritus. Therefore, we summarize here the present literature pointing to a close association between mast cells and sensory nerves in pruritic skin diseases as well as review the essential supporting findings on pruritic models in mice and rats.
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Affiliation(s)
- Hanna Siiskonen
- Department of Dermatology, Kuopio University Hospital and University of Eastern Finland, Kuopio, Finland
| | - Ilkka Harvima
- Department of Dermatology, Kuopio University Hospital and University of Eastern Finland, Kuopio, Finland
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39
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Svanström C, Lonne-Rahm SB, Nordlind K. Psoriasis and alcohol. PSORIASIS-TARGETS AND THERAPY 2019; 9:75-79. [PMID: 31687362 PMCID: PMC6709030 DOI: 10.2147/ptt.s164104] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 01/03/2019] [Accepted: 07/17/2019] [Indexed: 12/20/2022]
Abstract
Psoriasis is a chronic inflammatory skin disease that may be triggered or worsened by several factors, including alcohol. A higher than average alcohol consumption is common among individuals with psoriasis. Neurobiological signaling affected by alcohol intake includes a range of neurotransmitters, such as the dopaminergic, serotonergic, and tachykinergic systems, involved in reward and drug-seeking. These neurotransmitters may also have an impact on the inflammatory processes per se in psoriasis. Future therapy may, therefore, be targeted at neurotransmitter networks involved with both alcohol intake and the inflammatory processes.
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Affiliation(s)
- Caroline Svanström
- Department of Dermatology, Mälarsjukhuset, Eskilstuna, Sweden.,Department of Medicine, Solna, Dermatology and Venereology Unit, Karolinska Institutet, Stockholm, Sweden
| | | | - Klas Nordlind
- Department of Medicine, Solna, Dermatology and Venereology Unit, Karolinska Institutet, Stockholm, Sweden
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40
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Leon A, Rosen JD, Hashimoto T, Fostini AC, Paus R, Yosipovitch G. Itching for an answer: A review of potential mechanisms of scalp itch in psoriasis. Exp Dermatol 2019; 28:1397-1404. [DOI: 10.1111/exd.13947] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2018] [Revised: 04/03/2019] [Accepted: 04/08/2019] [Indexed: 01/01/2023]
Affiliation(s)
- Argentina Leon
- Dr Phillip Frost Department of Dermatology and Cutaneous Surgery Miami Itch Center Miller School of Medicine Miami Florida
| | - Jordan D. Rosen
- Dr Phillip Frost Department of Dermatology and Cutaneous Surgery Miami Itch Center Miller School of Medicine Miami Florida
| | - Takashi Hashimoto
- Dr Phillip Frost Department of Dermatology and Cutaneous Surgery Miami Itch Center Miller School of Medicine Miami Florida
| | - Anna C. Fostini
- Dr Phillip Frost Department of Dermatology and Cutaneous Surgery Miami Itch Center Miller School of Medicine Miami Florida
| | - Ralf Paus
- Dr Phillip Frost Department of Dermatology and Cutaneous Surgery Miami Itch Center Miller School of Medicine Miami Florida
| | - Gil Yosipovitch
- Dr Phillip Frost Department of Dermatology and Cutaneous Surgery Miami Itch Center Miller School of Medicine Miami Florida
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Abstract
Mast cells are best recognized for their role in allergy and anaphylaxis, but increasing evidence supports their role in neurogenic inflammation leading to pain and itch. Mast cells act as a "power house" by releasing algogenic and pruritogenic mediators, which initiate a reciprocal communication with specific nociceptors on sensory nerve fibers. Consequently, nerve fibers release inflammatory and vasoactive neuropeptides, which in turn activate mast cells in a feedback mechanism, thus promoting a vicious cycle of mast cell and nociceptor activation leading to neurogenic inflammation and pain/pruritus. Mechanisms underlying mast cell differentiation, activation, and intercellular interactions with inflammatory, vascular, and neural systems are deeply influenced by their microenvironment, imparting enormous heterogeneity and complexity in understanding their contribution to pain and pruritus. Neurogenic inflammation is central to both pain and pruritus, but specific mediators released by mast cells to promote this process may vary depending upon their location, stimuli, underlying pathology, gender, and species. Therefore, in this review, we present the contribution of mast cells in pathological conditions, including distressing pruritus exacerbated by psychologic stress and experienced by the majority of patients with psoriasis and atopic dermatitis and in different pain syndromes due to mastocytosis, sickle cell disease, and cancer.
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Affiliation(s)
- Kalpna Gupta
- Vascular Biology Center, Division of Hematology/Oncology/Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN, USA
| | - Ilkka T Harvima
- Department of Dermatology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland
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42
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Therianou A, Vasiadi M, Delivanis DA, Petrakopoulou T, Katsarou-Katsari A, Antoniou C, Stratigos A, Tsilioni I, Katsambas A, Rigopoulos D, Theoharides TC. Mitochondrial dysfunction in affected skin and increased mitochondrial DNA in serum from patients with psoriasis. Exp Dermatol 2019; 28:72-75. [PMID: 30390357 DOI: 10.1111/exd.13831] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2018] [Revised: 09/02/2018] [Accepted: 10/11/2018] [Indexed: 12/16/2022]
Abstract
Psoriasis is characterized by keratinocyte proliferation and chronic inflammation, but the pathogenesis is still unclear. Dysregulated mitochondria (mt) could lead to reduced apoptosis and extracellular secretion of mtDNA, acting as "innate pathogen" triggering inflammation. Serum was obtained from healthy volunteers and psoriatic patients. Mitochondrial DNA was extracted from the serum and amplified with quantitative PCR (qPCR). Punch biopsies were obtained from lesional and non-lesional psoriatic skin (10 cm apart) and from healthy volunteers, were placed in RNA later and were stored at -80°C until RNA was extracted and cDNA was synthesized; gene expression of uncoupling protein 2 (UCP2), Dynamin-related protein 1 (Drp1) and calcineurin, involved in the regulation of mitochondria function, was detected with qPCR. Mitochondrial DNA was significantly increased (7s, P = 0.0496 and Cytochrome B, CytB, P = 0.0403) in the serum of psoriatic patients (n = 63) as compared to controls (n = 27). Gene expression was significantly reduced for UCP2 (P = 0.0218), Drp1 (P = 0.0001) and calcineurin (P = 0.0001) in lesional psoriatic skin, as compared to non-lesional or control skin. Increased serum extracellular mtDNA in psoriatic patients and decreased expression of mitochondrial regulatory proteins in psoriatic skin suggest increased inflammation and reduced keratinocyte apoptosis, respectively. Inhibitors of mtDNA secretion and/or UCP2 stimulants may be potential treatment options.
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Affiliation(s)
- Anastasia Therianou
- Molecular Immunopharmacology and Drug Discovery Laboratory, Department of Immunology, Tufts University School of Medicine, Boston, Massachusetts
- First Department of Dermatology, Andreas Syggros Hospital of Cutaneous & Venereal Diseases, Athens University Medical School, Athens, Greece
| | - Magdalini Vasiadi
- Molecular Immunopharmacology and Drug Discovery Laboratory, Department of Immunology, Tufts University School of Medicine, Boston, Massachusetts
- General Anti-Cancer Hospital Agios Savvas, Athens, Greece
| | - Danae A Delivanis
- Molecular Immunopharmacology and Drug Discovery Laboratory, Department of Immunology, Tufts University School of Medicine, Boston, Massachusetts
| | | | - Alexandra Katsarou-Katsari
- First Department of Dermatology, Andreas Syggros Hospital of Cutaneous & Venereal Diseases, Athens University Medical School, Athens, Greece
| | - Christina Antoniou
- First Department of Dermatology, Andreas Syggros Hospital of Cutaneous & Venereal Diseases, Athens University Medical School, Athens, Greece
| | - Alexandros Stratigos
- First Department of Dermatology, Andreas Syggros Hospital of Cutaneous & Venereal Diseases, Athens University Medical School, Athens, Greece
| | - Irene Tsilioni
- Molecular Immunopharmacology and Drug Discovery Laboratory, Department of Immunology, Tufts University School of Medicine, Boston, Massachusetts
| | - Andreas Katsambas
- First Department of Dermatology, Andreas Syggros Hospital of Cutaneous & Venereal Diseases, Athens University Medical School, Athens, Greece
| | - Dimitris Rigopoulos
- First Department of Dermatology, Andreas Syggros Hospital of Cutaneous & Venereal Diseases, Athens University Medical School, Athens, Greece
| | - Theoharis C Theoharides
- Molecular Immunopharmacology and Drug Discovery Laboratory, Department of Immunology, Tufts University School of Medicine, Boston, Massachusetts
- Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, Massachusetts
- Department of Internal Medicine, Tufts University School of Medicine and Tufts Medical Center, Boston, Massachusetts
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43
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Lipitsä T, Siiskonen H, Naukkarinen A, Harvima IT. Mast cell chymase degrades fibrinogen and fibrin. Br J Dermatol 2018; 181:296-303. [PMID: 30561017 DOI: 10.1111/bjd.17534] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/12/2018] [Indexed: 11/29/2022]
Abstract
BACKGROUND The accumulation of immunoreactants and fibrinoid necrosis of postcapillary vessel walls are common pathological features of cutaneous immune complex vasculitis. In more advanced lesions, these immunoreactants are subject to proteolysis. Mast cell chymase is a powerful enzyme that can degrade several substrates including the extracellular matrix. Heparin can influence the catalytic properties of chymase. OBJECTIVES To study the effects of recombinant human (rh) chymase on fibrinogen, coagulation and fibrinolysis, and to relate these effects to the pathogenesis of vasculitis. METHODS The colocalization of chymase and fibrin in vasculitis specimens was analysed by immunohistochemical double staining. Fibrinogen and fibrin were treated with rh-chymase and the effects were studied in vitro by sodium dodecylsulfate polyacrylamide gel electrophoresis and a variety of clotting and fibrin gel experiments. The effects of rh-chymase on vasculitis cryosections were analysed by direct immunofluorescence. RESULTS Chymase-positive mast cells were associated with fibrin-positive vessels in vasculitis cryosections. Rh-chymase degraded the alpha-, beta- and gamma-chains of fibrinogen, while heparin enhanced the degradation of the beta-chain. Rh-chymase pretreatment of fibrinogen prolonged thrombin-induced clotting time. Fibrinogen degradation products induced by rh-chymase increased the clotting time of human plasma. Rh-chymase degraded fibrin gel prepared from fibrinogen or human plasma. Immunofluorescence staining positivity of fibrin in vasculitis cryosections decreased after pretreatment with rh-chymase for 24 h, and heparin enhanced this effect. CONCLUSIONS Mast cell chymase may constitute a previously unrecognized endogenous anticoagulant and fibrinolytic enzyme, and may be involved in the clearance of fibrin from vessel walls in aged vasculitis lesions.
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Affiliation(s)
- T Lipitsä
- Department of Dermatology, Kuopio University Hospital and University of Eastern Finland, Kuopio, Finland
| | - H Siiskonen
- Department of Dermatology, Kuopio University Hospital and University of Eastern Finland, Kuopio, Finland.,Cancer Center of Eastern Finland, University of Eastern Finland, Kuopio, Finland
| | - A Naukkarinen
- Department of Pathology, Kuopio University Hospital and University of Eastern Finland, Kuopio, Finland
| | - I T Harvima
- Department of Dermatology, Kuopio University Hospital and University of Eastern Finland, Kuopio, Finland.,Cancer Center of Eastern Finland, University of Eastern Finland, Kuopio, Finland
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44
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Babina M, Wang Z, Artuc M, Guhl S, Zuberbier T. MRGPRX2 is negatively targeted by SCF and IL-4 to diminish pseudo-allergic stimulation of skin mast cells in culture. Exp Dermatol 2018; 27:1298-1303. [PMID: 30091263 DOI: 10.1111/exd.13762] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2018] [Revised: 07/18/2018] [Accepted: 08/03/2018] [Indexed: 12/19/2022]
Abstract
MRGPRX2 was recently uncovered as the "missing link" in clinically relevant mast cell (MC) activation explaining previously puzzling phenomena. It is the receptor for various endogenous ligands and exogenous compounds alike, whose binding evokes rapid degranulation much like allergen-mediated exocytosis. While the perceivable outcomes are similar, the two activation routes differ regarding mechanism and regulation. We recently reported that acute SCF administration curbs responses evoked by MRGPRX2 in human skin MCs. Maintenance of MCs in culture requires the presence of MC supportive factors and renders the cells functionally and molecularly unequal to ex vivo counterparts. Here, we asked whether expansion in culture impacts the pseudo-allergic route, and if so, what contribution SCF and IL-4 play in this scenario. We report that the in vitro micromilieu dampens (but does not erase) pseudo-allergic responses and that this is accompanied by strongly reduced MRGPRX2 expression. Withdrawal of SCF or IL-4 individually, but most potently of both collectively, partially reinstates the MRGPRX2 pathway, revealing that SCF and IL-4 make negative adjustments to the pseudo-allergic pathway. Under all conditions, the FcεRI-triggered route showed the inverse pattern of regulation, substantiating that allergic and pseudo-allergic MC activation can obey opposite rules, hinting at possible competition between them.
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Affiliation(s)
- Magda Babina
- Department of Dermatology and Allergy, Allergy Center Charité, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany
| | - Zhao Wang
- Department of Dermatology and Allergy, Allergy Center Charité, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany
| | - Metin Artuc
- Department of Dermatology and Allergy, Allergy Center Charité, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany
| | - Sven Guhl
- Department of Dermatology and Allergy, Allergy Center Charité, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany
| | - Torsten Zuberbier
- Department of Dermatology and Allergy, Allergy Center Charité, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany
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45
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Peres LP, Oliveira FB, Cartell A, Mazzotti NG, Cestari TF. Density of mast cells and intensity of pruritus in psoriasis vulgaris: a cross sectional study. An Bras Dermatol 2018; 93:368-372. [PMID: 29924253 PMCID: PMC6001103 DOI: 10.1590/abd1806-4841.20186607] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2016] [Accepted: 03/16/2017] [Indexed: 11/22/2022] Open
Abstract
BACKGROUND Psoriasis is a chronic and prevalent disease, and the associated pruritus is a common, difficult-to-control symptom. The mediators involved in psoriatic pruritus have not been fully established. OBJECTIVE To evaluate associations between the number of mast cells in psoriatic lesions and the intensity of pruritus. METHODS 29 patients with plaque psoriasis were recruited. In all participants, Psoriasis Area and Severity Index and Body Surface Area were assessed. A questionnaire was administered to obtain clinical information and the Dermatology Life Quality Index. Pruritus was assessed using a visual analog scale and skin biopsies were performed for staining with Giemsa and Immunohistochemistry with C-Kit. RESULTS Pruritus was observed in 91.3% of our patients. Median VAS was 6 (p25-75: 2-8). The immunohistochemical method revealed a mean of 11.32 mast cells/field and Giemsa staining revealed a mean of 6.72 mast cells/field. There was no correlation between the intensity of pruritus and mast cell count, neither in Immunohistochemistry (p = 0.15; rho = -0.27) nor in Giemsa (p = 0.16; rho = -0.27). Pruritus did not impact on the Dermatology Life Quality Index (p = 0.51; rho = -0.13). STUDY LIMITATIONS The small sample size may be considered the main limitation of our study. CONCLUSIONS Although mast cells are mediators of pruritus in many cutaneous diseases, our findings support that psoriatic pruritus is a complex disorder with multifactorial, complex pathophysiology, involving pruritogenic mediators others than mast cells.
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Affiliation(s)
| | - Fabiana Bazanella Oliveira
- Service of Dermatology, Hospital de Clínicas de Porto
Alegre, Universidade Federal do Rio Grande do Sul (HCPA- UFRGS), Porto Alegre (RS),
Brazil
| | - André Cartell
- Service of Pathology, Hospital de Clínicas de Porto Alegre,
Universidade Federal do Rio Grande do Sul (HCPA- UFRGS), Porto Alegre (RS), Brazil
| | - Nicolle Gollo Mazzotti
- Service of Dermatology, Hospital de Clínicas de Porto
Alegre, Universidade Federal do Rio Grande do Sul (HCPA- UFRGS), Porto Alegre (RS),
Brazil
| | - Tania Ferreira Cestari
- Service of Dermatology, Hospital de Clínicas de Porto
Alegre, Universidade Federal do Rio Grande do Sul (HCPA- UFRGS), Porto Alegre (RS),
Brazil
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46
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Rousset L, Halioua B. Stress and psoriasis. Int J Dermatol 2018; 57:1165-1172. [DOI: 10.1111/ijd.14032] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2017] [Revised: 01/16/2018] [Accepted: 04/08/2018] [Indexed: 12/12/2022]
Affiliation(s)
- Laurie Rousset
- Dermatology Unit; Assistance Publique - Hôpitaux de Paris (AP-HP); Ile de France France
| | - Bruno Halioua
- Dermatology Unit; Institut Alfred Fournier; Paris France
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47
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New roles and controls of mast cells. Curr Opin Immunol 2018; 50:39-47. [DOI: 10.1016/j.coi.2017.10.012] [Citation(s) in RCA: 49] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2017] [Revised: 10/13/2017] [Accepted: 10/28/2017] [Indexed: 12/14/2022]
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48
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Patel AB, Tsilioni I, Weng Z, Theoharides TC. TNF stimulates IL-6, CXCL8 and VEGF secretion from human keratinocytes via activation of mTOR, inhibited by tetramethoxyluteolin. Exp Dermatol 2018; 27:135-143. [PMID: 29105195 DOI: 10.1111/exd.13461] [Citation(s) in RCA: 42] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/26/2017] [Indexed: 12/19/2022]
Abstract
Psoriasis is an autoimmune skin disease characterized by keratinocyte hyperproliferation and chronic inflammation. The pathogenesis of psoriasis involves proinflammatory cytokines, such as tumor necrosis factor (TNF), but the mechanism of keratinocyte activation is not well understood. Here, we show that TNF (10 or 50 ng/mL) stimulates a significant (P < .0001) gene expression and secretion of proinflammatory IL-6, CXCL8 and VEGF from both cultured human HaCaT and normal epidermal human keratinocytes (NHEKs). This effect occurs via activation of the mammalian target of rapamycin (mTOR) signalling complex as shown by Western blot analysis and phospho-ELISAs. Pretreatment with the novel natural flavonoid tetramethoxyluteolin (10-100 μmol L-1 ) significantly (P < .0001) inhibits gene expression and secretion (P < .0001) of all 3 mediators in a concentration-dependent manner. Moreover, tetramethoxyluteolin (50 μmol L-1 ) appears to be a potent inhibitor of the phosphorylated mTOR substrates (pmTORSer2448 , pp70S6KThr389 and p4EBP1Thr37/46 ) as compared to known mTOR inhibitors in keratinocytes. The present findings indicate that TNF stimulates skin inflammation via mTOR signalling. Inhibition by tetramethoxyluteolin may be used in the treatment for psoriasis.
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Affiliation(s)
- Arti B Patel
- Molecular Immunopharmacology and Drug Discovery Laboratory, Department of Integrative Physiology and Pathobiology, Tufts University School of Medicine, Boston, MA, USA.,Graduate Program in Cell, Molecular and Developmental Biology, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, MA, USA
| | - Irene Tsilioni
- Molecular Immunopharmacology and Drug Discovery Laboratory, Department of Integrative Physiology and Pathobiology, Tufts University School of Medicine, Boston, MA, USA
| | - Zuyi Weng
- Molecular Immunopharmacology and Drug Discovery Laboratory, Department of Integrative Physiology and Pathobiology, Tufts University School of Medicine, Boston, MA, USA
| | - Theoharis C Theoharides
- Molecular Immunopharmacology and Drug Discovery Laboratory, Department of Integrative Physiology and Pathobiology, Tufts University School of Medicine, Boston, MA, USA.,Graduate Program in Cell, Molecular and Developmental Biology, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, MA, USA.,Department of Internal Medicine, Tufts Medical Center, Tufts University School of Medicine, Boston, MA, USA
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49
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Han NR, Moon PD, Ryu KJ, Kim NR, Kim HM, Jeong HJ. Inhibitory effect of naringenin via IL-13 level regulation on thymic stromal lymphopoietin-induced inflammatory reactions. Clin Exp Pharmacol Physiol 2017; 45:362-369. [PMID: 29193236 DOI: 10.1111/1440-1681.12880] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2017] [Revised: 09/04/2017] [Accepted: 10/03/2017] [Indexed: 01/01/2023]
Abstract
Naringenin (NG) has various beneficial properties, such as anti-cancer and anti-inflammatory effects. Thymic stromal lymphopoietin (TSLP) induces mast cell proliferation and inflammatory reactions. The aim of this study was to investigate the regulatory effect of NG on TSLP-induced mast cell proliferation and inflammatory reactions using human mast cell line (HMC-1) cells. HMC-1 cells were pre-treated with NG and then treated with TSLP. HMC-1 cells proliferation was determined by quantifying bromodeoxyuridine incorporation. Levels of anti-apoptotic and pro-apoptotic factors were analyzed by western blot analysis. The productions and mRNA expressions of interleukin (IL)-13 and tumour necrosis factor-α (TNF-α) were analyzed by ELISA and quantitative real-time PCR. We found that NG significantly attenuated HMC-1 cells proliferation and Ki-67 mRNA expression promoted by TSLP. NG significantly suppressed mRNA expression of TSLP receptor and IL-7 receptor α in TSLP-treated HMC-1 cells. NG significantly down-regulated levels of phosphorylated-signal transducer and activation of transcription 6 and murine double-minute 2 in TSLP-treated HMC-1 cells, up-regulated levels of cleaved poly ADP-ribose polymerase and p53 in TSLP-treated HMC-1 cells. Furthermore, NG significantly decreased the productions and mRNA expressions of IL-13 and TNF-α in TSLP-treated HMC-1 cells. These results suggest NG has an inhibitory effect on mast cell-mediated allergic inflammatory reactions.
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Affiliation(s)
- Na-Ra Han
- Department of Pharmacology, College of Korean Medicine, Kyung Hee University, Seoul, Korea
| | - Phil-Dong Moon
- Center for Converging Humanities, Kyung Hee University, Seoul, Korea
| | - Ka-Jung Ryu
- Department of Pharmacology, College of Korean Medicine, Kyung Hee University, Seoul, Korea
| | - Na-Rae Kim
- Department of Pharmacology, College of Korean Medicine, Kyung Hee University, Seoul, Korea
| | - Hyung-Min Kim
- Department of Pharmacology, College of Korean Medicine, Kyung Hee University, Seoul, Korea
| | - Hyun-Ja Jeong
- Department of Food Science & Technology and Research Institute for Basic Science, Hoseo University, Asan, Chungnam, Korea
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50
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Antihistamines in the treatment of pruritus in psoriasis. Postepy Dermatol Alergol 2017; 34:457-463. [PMID: 29507561 PMCID: PMC5831281 DOI: 10.5114/ada.2017.71112] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2016] [Accepted: 07/11/2016] [Indexed: 01/13/2023] Open
Abstract
Aim To evaluate the efficacy of antihistamines in reducing pruritus in psoriasis, 61 patients were randomized to be treated for 1 week with clemastine (n = 20), levocetirizine (n = 21) or placebo (n = 20). Material and methods All patients received the same routine antipsoriatic treatment. Itch intensity was assessed with VAS and the Itch Questionnaire, and hand movements during sleep were counted with an accelerometer. Results There was a statistically significant decrease in mean VAS scoring in clemastine and levocetirizine groups (p < 0.001), but not in the placebo group. Questionnaire scoring decreased significantly during the study in all study groups, with the greatest improvement noted in the clemastine group. The number of wrist movements during sleep did not differ significantly between groups. Conclusions Antihistamines of the first and second generations seem to be effective in reducing itch in patients with psoriasis, albeit the antipruritic effect is rather moderate. These observations need to be confirmed on larger patient groups.
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