• colorectal cancer
• combination therapy
• helminth therapy
• helminth-derived products
• immune modulation
• precursors of colorectal cancer

• Humans
• Colorectal Neoplasms/immunology
• Colorectal Neoplasms/therapy
• Colorectal Neoplasms/parasitology
• Colorectal Neoplasms/genetics
• Animals
• Helminths/immunology
• Helminthiasis/immunology
• Immunomodulation
• Therapy with Helminths/methods
• Gene Editing

• National Natural Science Foundation of China
• Natural Science Foundation of Guangxi Province

• CELLULAR IMMUNOLOGY
• IBD CLINICAL

• Humans
• Immunotherapy/methods
• Immunotherapy, Adoptive/methods
• Immunotherapy, Adoptive/adverse effects
• Inflammatory Bowel Diseases/therapy
• Inflammatory Bowel Diseases/immunology
• Lymphocyte Depletion/methods
• T-Lymphocytes, Regulatory/immunology

• P30 DK097948 NIDDK NIH HHS
• R01 DK123233 NIDDK NIH HHS
• R01 DK132038 NIDDK NIH HHS
• U01 TR002997 NCATS NIH HHS

• autoimmunity
• gene editing
• immunotherapy
• induced Tregs
• transplantation

• T-Lymphocytes, Regulatory/immunology
• Humans
• Animals
• Autoimmunity
• Immunotherapy/methods
• Transplantation, Homologous
• Epigenesis, Genetic
• Autoimmune Diseases/immunology
• Autoimmune Diseases/therapy
• Graft Rejection/immunology
• Forkhead Transcription Factors/metabolism

• FORDECYT#302815 CONACyT

• postcoital inflammation
• semen
• seminal fluid

• EXPERIMENTAL COLITIS
• INFLAMMATORY BOWEL DISEASE
• MUCOSAL IMMUNOLOGY
• T LYMPHOCYTES

• Humans
• Animals
• Intraepithelial Lymphocytes/metabolism
• ATP Citrate (pro-S)-Lyase/metabolism
• CD8-Positive T-Lymphocytes/metabolism
• Colitis/metabolism
• Inflammatory Bowel Diseases
• Inflammation/metabolism
• Butyrates
• Intestinal Mucosa/metabolism
• Dextran Sulfate
• Disease Models, Animal

• CBir1
• CD45RBhi
• Th1
• Th17
• Treg

• Mice
• Animals
• Colitis/pathology
• Inflammatory Bowel Diseases/therapy
• Inflammatory Bowel Diseases/pathology
• CD4-Positive T-Lymphocytes/pathology
• Adoptive Transfer
• Disease Models, Animal

• R01 DK112436 NIDDK NIH HHS
• R01 DK125011 NIDDK NIH HHS
• R01 DK135193 NIDDK NIH HHS
• National Institutes of Health

• adoptive cellular therapies
• graft-versus-host-disease
• hematopoietic stem cell transplantation
• mesenchymal stromal cells
• regulatory T cells

• PRIMARY SCLEROSING CHOLANGITIS
• ULCERATIVE COLITIS

• Humans
• Cholangitis, Sclerosing/complications
• Cholangitis, Sclerosing/therapy
• Cholangitis, Sclerosing/diagnosis
• Colitis, Ulcerative/complications
• Colitis, Ulcerative/therapy
• Colitis, Ulcerative/diagnosis
• Intestinal Mucosa/metabolism
• T-Lymphocytes, Regulatory

• Deutsche Forschungsgemeinschaft

• chemokines
• colorectal cancer
• cytokines
• tumor-infiltrating lymphocytes

• Natural Science Foundation of Anhui Province
• National Natural Science Foundation of China

Expression of glycoprotein A dominant repeat (GARP) has been reported to occur only in activated human naturally occurring regulatory T cells (Tregs) and their clones, and not in activated effector T cells, indicating that GARP is a marker for bona fide Tregs. A different phenotype of chronic obstructive pulmonary disease (COPD) may have a different immunologic mechanism.

To investigate whether the distribution of Tregs defined by GARP is related to the multi-organ loss of tissue phenotype in COPD.

GARP expression on T cells from peripheral blood and bronchoalveolar lavage (BAL) collected from patients with COPD was examined by flow cytometry. The correlation of GARP expression to clinical outcomes and clinical phenotype, including the body mass index, lung function and quantitative computed tomography (CT) scoring of emphysema, was analyzed.

Patients with more baseline emphysema had lower forced expiratory volume, body mass index (BMI), worse functional capacity, and more osteoporosis, thus, resembling the multiple organ loss of tissue (MOLT) phenotype. Peripheral Foxp3⁺GARP⁺ Tregs are reduced in COPD patients, and this reduction reversely correlates with quartiles of CT emphysema severity in COPD. Meanwhile, the frequencies of Foxp3⁺GARP⁻ Tregs, which are characteristic of pro-inflammatory cytokine production, are significantly increased in COPD patients, and correlated with increasing quartiles of CT emphysema severity in COPD. Tregs in BAL show a similar pattern of variation in peripheral blood.

Decreased GARP expression reflects more advanced disease in MOLT phenotype of COPD. Our results have potential implications for better understanding of the immunological nature of COPD and the pathogenic events leading to lung damage.

The online version contains supplementary material available at 10.1186/s12931-022-02099-2.

• COPD
• Emphysema
• GARP
• MOLT
• T-regulatory cells

• diet
• epithelial barrier
• gut inflammation
• inflammatory bowel disease
• microbiome

• Adult
• Colitis, Ulcerative
• Crohn Disease
• Ethnicity
• Humans
• Inflammatory Bowel Diseases/etiology
• Inflammatory Bowel Diseases/therapy
• Minority Groups

• AGA Research Foundation (American Gastroenterological Association (AGA) Research Foundation)
• Leona M. and Harry B. Helmsley Charitable Trust (Helmsley)

Inflammatory bowel disease (IBD) is an increasingly urgent medical problem that strongly impairs quality of life for patients. A global rise in incidence has been observed over the last few decades, with the highest incidence rates recorded in North America and Europe. Still, an increased incidence has been reported in the last ten years in newly industrialized countries in Asia, including China and India, both with more than one billion inhabitants. These data underline that IBD is an urgent global health problem. In addition, it is estimated that between 20% and 30% of IBD patients will develop colorectal cancer (CRC) within their lifetime and CRC mortality is approximately 50% amongst IBD patients. Although the exact etiology of IBD is still being defined, it is thought to be due to a complex interaction between many factors, including defects in the innate and adaptive immune system; microbial dysbiosis, i.e., abnormal levels of, or abnormal response to, the gastrointestinal microbiome; a genetic predisposition; and several environmental factors. At present, however, it is not fully understood which of these factors are the initiators of inflammation and which are compounders. The purpose of this review is to analyze the complex balance that exists between these elements to maintain intestinal homeostasis and prevent IBD or limit adverse effects on people’s health.

• Dysbiosis/complications
• Gastrointestinal Microbiome
• Humans
• Inflammatory Bowel Diseases
• Intestines
• Quality of Life

Currently, it is unclear whether Sishen Wan (SSW) could modulate the balance of Th1 cells, Th17 cells, and Tregs and we evaluated the effects of SSW on T cell responses in mice models of ulcerative colitis (UC). The mice models of acute UC (4% dextran sodium sulfate (DSS), 8 days) and chronic UC (3% DSS, 16 days) with SSW were assayed. Colon tissues were collected for immunohistochemical analysis, enzyme linked immunosorbent assay (ELISA), and flow cytometry (FCM). The expressions of cytokines associated with Tregs, transcription factors of Th17 cells, the frequencies of Th1 cells, Th17 cells, and Tregs, and the functional plasticity of Th17 cells were detected. The frequency of IFN-γ⁺ T cells was not changed significantly with SSW treatment in acute DSS. In chronic models, the frequency of IFN-γ⁺ T cells was downregulated with SSW. Meanwhile, the levels of RORγt and the frequency of IL-17A⁺ Th17 cells showed no significant differences after SSW treatment. Despite no significant effect on the transdifferentiation of Th17 cells in chronic UC models, SSW transdifferentiated Th17 cells into IL-10⁺ Th17 cells and downregulated IFN-γ⁺ Th17 cells/IL-10⁺ Th17 cells in acute DSS. Moreover, there were no significant changes of cytokines secreted by Tregs in acute DSS after SSW treatment, but SSW facilitated the expressions of IL-10 and IL-35, as well as development of IL-10⁺ Tregs in chronic DSS. SSW showed depressive effects on the immunoreaction of Th17 cells and might promote the conversion of Th17 cells into IL-10⁺ Th17 cells in acute UC, while it inhibited the excessive reaction of Th1 cells, facilitated the development of Tregs, and enhanced the anti-inflammatory effects in chronic UC.

Atherosclerotic plaque instability contributes to ischaemic stroke and myocardial infarction. This study is to compare the abundance and difference of immune cell subtypes within unstable atherosclerotic tissues. CIBERSORT was used to speculate the proportions of 22 immune cell types based on a microarray of atherosclerotic carotid artery samples. R software was utilized to illustrate the bar plot, heat map and vioplot. The immune cell landscape in atherosclerosis was diverse, dominated by M2 macrophages, M0 macrophages, resting CD4 memory T cells and CD8 T cells. There was a significant difference in resting CD4 memory T cells (p = 0.032), T cells follicular helper (p = 0.033), M0 (p = 0.047) and M2 macrophages (p = 0.012) between stable and unstable atherosclerotic plaques. Compared with stable atherosclerotic plaques, unstable atherosclerotic plaques had a higher percentage of M2 macrophages. Moreover, correlation analysis indicated that the percentage of naïve CD4 T cells was strongly correlated with that of gamma delta T cells (r = 0.93, p < 0.001), while memory B cells were correlated with plasma cells (r = 0.85, p < 0.001). In summary, our study explored the abundance and difference of specific immune cell subgroups at unstable plaques, which would aid new immunotherapies for atherosclerosis.

• CIBERSORT
• M2 macrophages
• carotid artery atherosclerosis
• immune infiltration
• unstable atherosclerosis

• Extracellular vesicles
• Treg/Th17 cell balance
• gut microbiome
• intestinal immunity
• ulcerative colitis

• Animals
• China
• Colitis/drug therapy
• Colitis, Ulcerative/drug therapy
• Colitis, Ulcerative/metabolism
• Colon/drug effects
• Cytokines/metabolism
• Disease Models, Animal
• Extracellular Vesicles/genetics
• Extracellular Vesicles/metabolism
• Extracellular Vesicles/physiology
• Gastrointestinal Microbiome/drug effects
• Inflammatory Bowel Diseases/drug therapy
• Intestinal Mucosa/metabolism
• Intestines/metabolism
• Male
• Mice
• Mice, Inbred C57BL
• Milk/metabolism
• NF-kappa B/metabolism
• RAW 264.7 Cells
• RNA, Ribosomal, 16S/genetics
• Signal Transduction
• T-Lymphocytes, Regulatory/metabolism
• Th17 Cells/metabolism

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract that consists of Crohn’s disease (CD) and ulcerative colitis (UC). Cytokines are thought to be key mediators of inflammation-mediated pathological processes of IBD. These cytokines play a crucial role through the Janus kinase (JAK) and signal transducer and activator of transcription (STAT) signaling pathways. Several small molecules inhibiting JAK have been used in clinical trials, and one of them has been approved for IBD treatment. Many anti-inflammatory phytochemicals have been shown to have potential as new drugs for IBD treatment. This review describes the significance of the JAK–STAT pathway as a current therapeutic target for IBD and discusses the recent findings that phytochemicals can ameliorate disease symptoms by affecting the JAK–STAT pathway in vivo in IBD disease models. Thus, we suggest that phytochemicals modulating JAK–STAT pathways are potential candidates for developing new therapeutic drugs, alternative medicines, and nutraceutical agents for the treatment of IBD.

• inflammatory bowel disease (IBD)
• janus kinase (JAK)
• phytochemicals
• signal transducer and activator of transcription (STAT)

Previous data have reported that the growth of established tumors may be facilitated by postsepsis disorder through changes in the microenvironment and immune dysfunction. However, the influence of postsepsis disorder in initial carcinogenesis remains elusive.

In the present work, the effect of postsepsis on inflammation-induced early carcinogenesis was evaluated in an experimental model of colitis-associated colorectal cancer (CAC). We also analyzed the frequency and role of intestinal T regulatory cells (Treg) in CAC carcinogenesis.

The colitis grade and the tumor development rate were evaluated postmortem or in vivo through serial colonoscopies. Sepsis-surviving mice (SSM) presented with a lower colonic DNA damage, polyp incidence, reduced tumor load, and milder colitis than their sham-operated counterparts. Ablating Treg led to restoration of the ability to develop colitis and tumor polyps in the SSM, in a similar fashion to that in the sham-operated mice. On the other hand, the growth of subcutaneously inoculated MC38luc colorectal cancer cells or previously established chemical CAC tumors was increased in SSM.

Our results provide evidence that postsepsis disorder has a dual effect in cancer development, inhibiting inflammation-induced early carcinogenesis in a Treg-dependent manner, while increasing the growth of previously established tumors.

• T-lymphocytes
• cytokines
• immunology
• oncology
• tumor microenvironment

• post-translational modifications
• chronic inflammation

• Chronic Disease
• Hippo Signaling Pathway
• Humans
• Inflammation/genetics
• Inflammatory Bowel Diseases/pathology
• Protein Processing, Post-Translational/genetics
• Protein Serine-Threonine Kinases/genetics

• Guangzhou Science, Technology and Innovation Commission (Bureau of Science and Information Technology of Guangzhou Municipality)
• National Natural Science Foundation of China (National Science Foundation of China)
• Guangdong Science and Technology Department (Science and Technology Department, Guangdong Province)
• Fundamental Research Funds for the Central Universities (#19ykzd11)

• Crohn’s disease
• Inflammatory bowel disease
• JAK/STAT inhibition
• JAK/STAT pathway
• Janus kinase
• Signal transducer and activator of transcription
• Tofacitinib
• Ulcerative colitis

• Colitis, Ulcerative/drug therapy
• Crohn Disease/drug therapy
• Humans
• Janus Kinase Inhibitors/pharmacology
• Janus Kinase Inhibitors/therapeutic use
• Janus Kinases
• Transducers

• Biologicals
• Crohn’s disease
• Cytokines
• Gastroenterology
• IBD
• Ulcerative colitis

• Rural Development Administration, Republic of Korea

• Anti-idiotypic immunoregulation
• Immunotherapy
• Inflammatory colitis

• Adaptive Immunity
• Animals
• Arthritis, Rheumatoid/immunology
• Humans
• Immune System
• Immunity, Innate
• Inflammation
• Inflammatory Bowel Diseases/immunology
• Neuroimmunomodulation
• Reflex

• Autoimmunity diseases
• CD4+
• CD8+
• Cancer immunotherapy
• OX40
• Treg

Regulatory T cells (Tregs) are essential for the maintenance of gut homeostasis by suppressing conventional CD4⁺ helper T cells (Tconvs) that are activated by microbial antigens. Although thymus is the major source of the peripheral Tregs, peripheral conversion from Tconvs to Tregs have also been shown to occur under various experimental conditions. It remains less clear about the frequency of lineage conversion from Tconvs to Tregs in naïve animals. Here we used a newly established reporter system to track a group of post expansion Tregs (eTregs), which exhibited a stronger suppressive ability than the non-lineage marked Tregs. Notably, microbial antigens are the primary driver for the formation of eTregs. TCR repertoire analysis of Peyer's patch T cells revealed that eTregs are clonally related to Tconvs, but not to the non-lineage tracked Tregs. Adoptive transfer of Tconvs into lymphopenic hosts demonstrated a conversion from Tconvs to eTregs. Thus, our lineage tracking method was able to capture the lineage conversion from microbial activated effector T cells to Tregs in naïve animals. This study suggests that a fraction of clonally activated T cells from the natural T cell repertoire exhibits lineage conversion to Tregs in response to commensal microbes under homeostatic conditions.

• TCR repertoire
• gut
• inducible Tregs
• microbiota
• tolerance

• Animal studies
• Autoimmune diseases
• Gene modulation
• Immunopathogenesis

• CD4+CD25+CD127low regulatory T cells
• cytokines
• flow cytometry
• peripheral blood
• primary hepatic carcinoma

• Adult
• Biopsy
• CD4 Antigens/blood
• Carcinoma, Hepatocellular/blood
• Carcinoma, Hepatocellular/immunology
• Carcinoma, Hepatocellular/pathology
• Female
• Flow Cytometry
• Humans
• Interleukin-10/blood
• Interleukin-2 Receptor alpha Subunit/blood
• Interleukin-7 Receptor alpha Subunit/blood
• Liver/metabolism
• Liver/pathology
• Liver Neoplasms/blood
• Liver Neoplasms/immunology
• Liver Neoplasms/pathology
• Male
• Middle Aged
• T-Lymphocytes, Regulatory/immunology
• T-Lymphocytes, Regulatory/metabolism
• Transforming Growth Factor beta1/blood

• CD4(+) T cell
• Estrogen receptor β
• Inflammatory bowel disease
• Regulatory T cell

• Adult
• Animals
• Anti-Inflammatory Agents
• CD4-Positive T-Lymphocytes/metabolism
• CD8-Positive T-Lymphocytes/metabolism
• Case-Control Studies
• Cell Differentiation/physiology
• Cell Proliferation/physiology
• Colitis/chemically induced
• Colitis/metabolism
• Colon/drug effects
• Colon/metabolism
• Dextran Sulfate/pharmacology
• Disease Models, Animal
• Estrogen Receptor beta/metabolism
• Female
• Humans
• Inflammation/metabolism
• Lymphocyte Activation/physiology
• Male
• Mice
• Mice, Inbred C57BL
• Signal Transduction/physiology
• Smad Proteins/metabolism
• T-Lymphocytes, Regulatory/metabolism
• Transforming Growth Factor beta1/metabolism

• Crohn's disease, ulcerative colitis
• anti-integrin therapy
• inflammatory bowel disease
• integrins

• AhR
• Cell differentiation
• Dioxin
• Helper T cell
• Immune suppression
• TCDD

The uncontrolled activation of the immune system toward antigens contained in the gut lumen in genetically predisposed subjects is believed to be the leading cause of inflammatory bowel disease (IBD). Two not mutually exclusive hypotheses can explain the pathogenic process leading to IBD. The first and mostly explored hypothesis states that the loss of tolerance toward gut microbiota antigens generates an aberrant inflammatory response that is perpetuated by continuous and unavoidable exposure to the triggering antigens. However, the discovery that the resolution of inflammation is not the mere consequence of clearing inflammatory triggers and diluting pro-inflammatory factors, but rather an active process in which molecular and cellular elements are involved, implies that a defect in the pro-resolving mechanisms might cause chronic inflammation in different immune-mediated diseases, including IBD. Here we review data on pro-resolving and counter-regulatory mechanisms involved in the resolution of inflammation, aiming to identify their possible involvement in the pathogenesis of IBD.

• colitis
• counter-regulatory mechanisms
• immunosuppression
• resolution

• Animals
• Gastrointestinal Microbiome
• Humans
• Immune Tolerance
• Inflammation/complications
• Inflammation/immunology
• Inflammatory Bowel Diseases/etiology
• Inflammatory Bowel Diseases/immunology
• Intestinal Mucosa/microbiology
• Intestinal Mucosa/pathology
• Intestines/microbiology
• Intestines/pathology
• Mice

• FoxP3/GARP/LAP
• HLA-II
• T regulatory cells
• group A streptococcus

• Animals
• Cell Differentiation/immunology
• Colitis/immunology
• Colitis/metabolism
• DNA-Binding Proteins/metabolism
• Forkhead Transcription Factors/genetics
• Forkhead Transcription Factors/metabolism
• Gene Deletion
• Gene Expression
• Histones/metabolism
• Inflammation
• Intestinal Mucosa/immunology
• Intestinal Mucosa/pathology
• Mice
• Mice, Inbred C57BL
• Neuropilin-1/metabolism
• Regulatory Sequences, Nucleic Acid
• Repressor Proteins/genetics
• Repressor Proteins/metabolism
• T-Lymphocytes, Regulatory/immunology
• T-Lymphocytes, Regulatory/physiology
• Transcription Factors/metabolism

• Inflammatory bowel diseases
• Pim-1 kinase
• Pim-1 kinase inhibitor
• T-cells

• immune system
• inflammatory bowel diseases
• intestinal epithelium
• lymphocytes
• mucosal immunity