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      The Function and Role of the Th17/Treg Cell Balance in Inflammatory Bowel Disease

      review-article
      , , ,
      Journal of Immunology Research
      Hindawi

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          Abstract

          Inflammatory bowel disease (IBD) is a chronic, inflammatory, and autoimmune disorder. The pathogenesis of IBD is not yet clear. Studies have shown that the imbalance between T helper 17 (Th17) and regulatory T (Treg) cells, which differentiate from CD4 + T cells, contributes to IBD. Th17 cells promote tissue inflammation, and Treg cells suppress autoimmunity in IBD. Therefore, Th17/Treg cell balance is crucial. Some regulatory factors affecting the production and maintenance of these cells are also important for the proper regulation of the Th17/Treg balance; these factors include T cell receptor (TCR) signaling, costimulatory signals, cytokine signaling, bile acid metabolites, and the intestinal microbiota. This article focuses on our understanding of the function and role of the balance between Th17/Treg cells in IBD and these regulatory factors and their clinical significance in IBD.

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          Most cited references81

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          The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis.

          Regulatory T cells (Tregs) that express the transcription factor Foxp3 are critical for regulating intestinal inflammation. Candidate microbe approaches have identified bacterial species and strain-specific molecules that can affect intestinal immune responses, including species that modulate Treg responses. Because neither all humans nor mice harbor the same bacterial strains, we posited that more prevalent factors exist that regulate the number and function of colonic Tregs. We determined that short-chain fatty acids, gut microbiota-derived bacterial fermentation products, regulate the size and function of the colonic Treg pool and protect against colitis in a Ffar2-dependent manner in mice. Our study reveals that a class of abundant microbial metabolites underlies adaptive immune microbiota coadaptation and promotes colonic homeostasis and health.
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            Short Chain Fatty Acids (SCFAs)-Mediated Gut Epithelial and Immune Regulation and Its Relevance for Inflammatory Bowel Diseases

            Ulcerative colitis (UC) and Crohn's disease (CD), collectively known as Inflammatory Bowel Diseases (IBD), are caused by a complex interplay between genetic, immunologic, microbial and environmental factors. Dysbiosis of the gut microbiome is increasingly considered to be causatively related to IBD and is strongly affected by components of a Western life style. Bacteria that ferment fibers and produce short chain fatty acids (SCFAs) are typically reduced in mucosa and feces of patients with IBD, as compared to healthy individuals. SCFAs, such as acetate, propionate and butyrate, are important metabolites in maintaining intestinal homeostasis. Several studies have indeed shown that fecal SCFAs levels are reduced in active IBD. SCFAs are an important fuel for intestinal epithelial cells and are known to strengthen the gut barrier function. Recent findings, however, show that SCFAs, and in particular butyrate, also have important immunomodulatory functions. Absorption of SCFAs is facilitated by substrate transporters like MCT1 and SMCT1 to promote cellular metabolism. Moreover, SCFAs may signal through cell surface G-protein coupled receptors (GPCRs), like GPR41, GPR43, and GPR109A, to activate signaling cascades that control immune functions. Transgenic mouse models support the key role of these GPCRs in controlling intestinal inflammation. Here, we present an overview of microbial SCFAs production and their effects on the intestinal mucosa with specific emphasis on their relevance for IBD. Moreover, we discuss the therapeutic potential of SCFAs for IBD, either applied directly or by stimulating SCFAs-producing bacteria through pre- or probiotic approaches.
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              A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17.

              Interleukin 17 (IL-17) has been linked to autoimmune diseases, although its regulation and function have remained unclear. Here we have evaluated in vitro and in vivo the requirements for the differentiation of naive CD4 T cells into effector T helper cells that produce IL-17. This process required the costimulatory molecules CD28 and ICOS but was independent of the cytokines and transcription factors required for T helper type 1 or type 2 differentiation. Furthermore, both IL-4 and interferon-gamma negatively regulated T helper cell production of IL-17 in the effector phase. In vivo, antibody to IL-17 inhibited chemokine expression in the brain during experimental autoimmune encephalomyelitis, whereas overexpression of IL-17 in lung epithelium caused chemokine production and leukocyte infiltration. Thus, IL-17 expression characterizes a unique T helper lineage that regulates tissue inflammation.
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                Author and article information

                Contributors
                Journal
                J Immunol Res
                J Immunol Res
                JIR
                Journal of Immunology Research
                Hindawi
                2314-8861
                2314-7156
                2020
                15 December 2020
                : 2020
                : 8813558
                Affiliations
                The Second Central Laboratory, Key Laboratory of Integrative Chinese and Western Medicine for the Diagnosis and Treatment of Circulatory Diseases of Zhejiang Province, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, China
                Author notes

                Academic Editor: Jie Tian

                Author information
                https://orcid.org/0000-0001-5014-7156
                https://orcid.org/0000-0002-7519-0844
                https://orcid.org/0000-0002-2072-444X
                https://orcid.org/0000-0001-6170-8481
                Article
                10.1155/2020/8813558
                7755495
                33381606
                e041c9df-4da9-47a8-a315-a9b0b6425fc6
                Copyright © 2020 Jun-bin Yan et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 13 August 2020
                : 28 September 2020
                : 9 December 2020
                Funding
                Funded by: Zhejiang Provincial Key Lab of Diagnosis and Treatment of Circulatory Diseases
                Award ID: 2019E10012
                Funded by: Zhejiang Chinese Medical University
                Award ID: 2019ZG03
                Funded by: Zhejiang Traditional Chinese Medicine Administration
                Award ID: 2020ZB081
                Funded by: Health Commission of Zhejiang Province
                Award ID: 2018KY550
                Funded by: Natural Science Foundation of Zhejiang Province
                Award ID: LY17H290007
                Categories
                Review Article

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