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      MAIT Cells in Barrier Tissues: Lessons from Immediate Neighbors

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          Abstract

          Mucosal-associated invariant T (MAIT) cells are innate-like T cells present at considerable frequencies in human blood and barrier tissues, armed with an expanding array of effector functions in response to homeostatic perturbations. Analogous to other barrier immune cells, their phenotype and function is driven by crosstalk with host and dynamic environmental factors, most pertinently the microbiome. Given their distribution, they must function in diverse extracellular milieus. Tissue-specific and adapted functions of barrier immune cells are shaped by transcriptional programs and regulated through a blend of local cellular, inflammatory, physiological, and metabolic mediators unique to each microenvironment. This review compares the phenotype and function of MAIT cells with other barrier immune cells, highlighting potential areas for future exploration. Appreciation of MAIT cell biology within tissues is crucial to understanding their niche in health and disease.

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          Most cited references238

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          Origin and physiological roles of inflammation.

          Inflammation underlies a wide variety of physiological and pathological processes. Although the pathological aspects of many types of inflammation are well appreciated, their physiological functions are mostly unknown. The classic instigators of inflammation - infection and tissue injury - are at one end of a large range of adverse conditions that induce inflammation, and they trigger the recruitment of leukocytes and plasma proteins to the affected tissue site. Tissue stress or malfunction similarly induces an adaptive response, which is referred to here as para-inflammation. This response relies mainly on tissue-resident macrophages and is intermediate between the basal homeostatic state and a classic inflammatory response. Para-inflammation is probably responsible for the chronic inflammatory conditions that are associated with modern human diseases.
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            From Dietary Fiber to Host Physiology: Short-Chain Fatty Acids as Key Bacterial Metabolites.

            A compelling set of links between the composition of the gut microbiota, the host diet, and host physiology has emerged. Do these links reflect cause-and-effect relationships, and what might be their mechanistic basis? A growing body of work implicates microbially produced metabolites as crucial executors of diet-based microbial influence on the host. Here, we will review data supporting the diverse functional roles carried out by a major class of bacterial metabolites, the short-chain fatty acids (SCFAs). SCFAs can directly activate G-coupled-receptors, inhibit histone deacetylases, and serve as energy substrates. They thus affect various physiological processes and may contribute to health and disease.
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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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                Author and article information

                Contributors
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                30 November 2020
                2020
                : 11
                : 584521
                Affiliations
                [1] 1 Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford , Oxford, United Kingdom
                [2] 2 Peter Medawar Building for Pathogen Research, University of Oxford , Oxford, United Kingdom
                Author notes

                Edited by: Edwin Leeansyah, Tsinghua-Berkeley Shenzhen Institute, China

                Reviewed by: Megan K. L. MacLeod, University of Glasgow, United Kingdom; Dominic Paquin Proulx, United States Military HIV Research Program, United States; Shouxiong Huang, University of Cincinnati, United States

                *Correspondence: Ali Amini, ali.amini@ 123456sjc.ox.ac.uk ; Paul Klenerman, paul.klenerman@ 123456medawar.ox.ac.uk

                This article was submitted to Mucosal Immunity, a section of the journal Frontiers in Immunology

                Article
                10.3389/fimmu.2020.584521
                7734211
                33329559
                9d4506fd-8848-43ba-a720-29ebef84d83d
                Copyright © 2020 Amini, Pang, Hackstein and Klenerman

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 17 July 2020
                : 26 October 2020
                Page count
                Figures: 2, Tables: 2, Equations: 0, References: 238, Pages: 20, Words: 9207
                Funding
                Funded by: Wellcome Trust 10.13039/100004440
                Award ID: 216417/Z/19/Z, WT109965MA
                Funded by: National Institutes of Health 10.13039/100000002
                Award ID: U19 I082360
                Funded by: NIHR Oxford Biomedical Research Centre 10.13039/501100013373
                Funded by: Deutsche Forschungsgemeinschaft 10.13039/501100001659
                Award ID: 403193363
                Categories
                Immunology
                Review

                Immunology
                mucosal-associated invariant t cells,microenvironment,microbiome,metabolism,tissue resident cells,mucosal immunology,diet

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