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      Biological functions of MAIT cells in tissues

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          Abstract

          Mucosal associated invariant T (MAIT) cells have a recognised innate-like capacity for antibacterial host defence, consequent on the specificity of their T cell receptor (TCR) for small molecule metabolites produced by a range of prokaryotic and fungal species, their effector memory phenotype, and their expression of cytotoxic molecules. However, recent studies have identified at least two other important functions of MAIT cells in antiviral immunity and in tissue homeostasis and repair. Each are related to distinct transcriptional programmes, which are activated differentially according to the specific immune context. Here we discuss these diverse functions, we review the evidence for the newly identified role of MAIT cells in promoting tissue repair, and we discuss emerging data pointing to the future directions of MAIT cell research including roles in cancer, in antiviral immunity and recent studies in the immune response to SARS-CoV-2 infection. Overall these studies have made us aware of the potential for pleiotropic roles of MAIT cells and related cell populations in micee and humans, and have created a simple and attractive new paradigm for regulation in barrier tissues, where antigen and tissue damage are sensed, integrated and interpreted.

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          Most cited references31

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          The Immunological Genome Project: networks of gene expression in immune cells.

          The Immunological Genome Project combines immunology and computational biology laboratories in an effort to establish a complete 'road map' of gene-expression and regulatory networks in all immune cells.
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            Is Open Access

            Comprehensive mapping of immune perturbations associated with severe COVID-19

            Although critical illness has been associated with SARS-CoV-2-induced hyperinflammation, the immune correlates of severe COVID-19 remain unclear. Here, we comprehensively analyzed peripheral blood immune perturbations in 42 SARS-CoV-2 infected and recovered individuals. We identified extensive induction and activation of multiple immune lineages, including T cell activation, oligoclonal plasmablast expansion, and Fc and trafficking receptor modulation on innate lymphocytes and granulocytes, that distinguished severe COVID-19 cases from healthy donors or SARS-CoV-2-recovered or moderate severity patients. We found the neutrophil to lymphocyte ratio to be a prognostic biomarker of disease severity and organ failure. Our findings demonstrate broad innate and adaptive leukocyte perturbations that distinguish dysregulated host responses in severe SARS-CoV-2 infection and warrant therapeutic investigation.
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              MAIT cells are imprinted by the microbiota in early life and promote tissue repair

              How early-life colonization and subsequent exposure to the microbiota affect long-term tissue immunity remains poorly understood. Here, we show that the development of mucosal-associated invariant T (MAIT) cells relies on a specific temporal window, after which MAIT cell development is permanently impaired. This imprinting depends on early-life exposure to defined microbes that synthesize riboflavin-derived antigens. In adults, cutaneous MAIT cells are a dominant population of interleukin-17A (IL-17A)–producing lymphocytes, which display a distinct transcriptional signature and can subsequently respond to skin commensals in an IL-1–, IL-18–, and antigen-dependent manner. Consequently, local activation of cutaneous MAIT cells promotes wound healing. Together, our work uncovers a privileged interaction between defined members of the microbiota and MAIT cells, which sequentially controls both tissue-imprinting and subsequent responses to injury.
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                Author and article information

                Journal
                Mol Immunol
                Mol Immunol
                Molecular Immunology
                Elsevier Ltd.
                0161-5890
                1872-9142
                25 December 2020
                February 2021
                25 December 2020
                : 130
                : 154-158
                Affiliations
                [a ]Peter Medawar Building for Pathogen Research, South Parks Road, Oxford, OX1 3SY, UK
                [b ]National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC), John Radcliffe Hospital, Oxford, OX3 9DU, UK
                [c ]Translational Gastroenterology Unit, John Radcliffe Hospital, Oxford, OX3 9DU, UK
                [d ]Respiratory Medicine Unit, Nuffield Department of Medicine Experimental Medicine, University of Oxford, OX3 9DU, Oxfordshire, UK
                [e ]Department of Microbiology and Immunology, University of Otago, Dunedin, 9054, Otago, New Zealand
                [f ]Southern Community Laboratories, Dunedin, 9016, Otago, New Zealand
                Author notes
                [* ]Corresponding author at: Peter Medawar Building for Pathogen Research, South Parks Road, Oxford, OX1 3SY, UK.
                Article
                S0161-5890(20)30578-2
                10.1016/j.molimm.2020.12.017
                8021939
                33358567
                5690fcb3-dc73-4d16-9273-6cf653467a83
                © 2020 Elsevier Ltd. All rights reserved.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                : 30 November 2020
                : 7 December 2020
                Categories
                Article

                Immunology
                5-op-ru, 5-(2-oxopropylideneamino)-6-d-ribitylaminouracil,5-a-ru, 5-amino-6-d-ribitylaminouracil,covid-19, coronavirus disease-19,gsea, gene set enrichment analysis,inkt, invariant natural killer t,mait, mucosal associated invariant t,sars-cov-2, severe acute respiratory syndrome coronavirus 2,tc17, type-17 cd8+ t cells,mait cell,inkt cell,virus,covid-19,sars-cov-2,tissue repair

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