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A critical role for regulatory T cell–mediated control of inflammation in the absence of commensal microbiota
Suppression mediated by regulatory T cells (T reg cells) represents a unique, cell-extrinsic mechanism of in-trans negative regulation that restrains multiple types of immune cells. The loss of T reg cells leads to fatal, highly aggressive, and widespread immune-mediated lesions. This severe autoimm...
Autores principales: | , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2964571/ https://www.ncbi.nlm.nih.gov/pubmed/20921284 http://dx.doi.org/10.1084/jem.20101235 |
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author | Chinen, Takatoshi Volchkov, Pavel Y. Chervonsky, Alexander V. Rudensky, Alexander Y. |
author_facet | Chinen, Takatoshi Volchkov, Pavel Y. Chervonsky, Alexander V. Rudensky, Alexander Y. |
author_sort | Chinen, Takatoshi |
collection | PubMed |
description | Suppression mediated by regulatory T cells (T reg cells) represents a unique, cell-extrinsic mechanism of in-trans negative regulation that restrains multiple types of immune cells. The loss of T reg cells leads to fatal, highly aggressive, and widespread immune-mediated lesions. This severe autoimmunity may be driven by commensal microbiota, the largest source of non-self ligands activating the innate and adaptive immune systems. Alternatively, T reg cells may primarily restrain T cells with a diverse self–major histocompatibility complex (MHC)–restricted T cell receptor repertoire independently of commensal microbiota. In this study, we demonstrate that in germ-free (GF) mice, ablation of the otherwise fully functional T reg cells resulted in a systemic autoimmune lympho- and myeloproliferative syndrome and tissue inflammation comparable with those in T reg cell–ablated conventional mice. Importantly, there were two exceptions: in GF mice deprived of T reg cells, the inflammation in the small intestine was delayed, whereas exocrine pancreatitis was markedly accelerated compared with T reg cell–ablated conventional mice. These findings suggest that the main function of T reg cells is restraint of self-MHC–restricted T cell responsiveness, which, regardless of the presence of commensal microbiota, poses a threat of autoimmunity. |
format | Text |
id | pubmed-2964571 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-29645712011-04-25 A critical role for regulatory T cell–mediated control of inflammation in the absence of commensal microbiota Chinen, Takatoshi Volchkov, Pavel Y. Chervonsky, Alexander V. Rudensky, Alexander Y. J Exp Med Brief Definitive Report Suppression mediated by regulatory T cells (T reg cells) represents a unique, cell-extrinsic mechanism of in-trans negative regulation that restrains multiple types of immune cells. The loss of T reg cells leads to fatal, highly aggressive, and widespread immune-mediated lesions. This severe autoimmunity may be driven by commensal microbiota, the largest source of non-self ligands activating the innate and adaptive immune systems. Alternatively, T reg cells may primarily restrain T cells with a diverse self–major histocompatibility complex (MHC)–restricted T cell receptor repertoire independently of commensal microbiota. In this study, we demonstrate that in germ-free (GF) mice, ablation of the otherwise fully functional T reg cells resulted in a systemic autoimmune lympho- and myeloproliferative syndrome and tissue inflammation comparable with those in T reg cell–ablated conventional mice. Importantly, there were two exceptions: in GF mice deprived of T reg cells, the inflammation in the small intestine was delayed, whereas exocrine pancreatitis was markedly accelerated compared with T reg cell–ablated conventional mice. These findings suggest that the main function of T reg cells is restraint of self-MHC–restricted T cell responsiveness, which, regardless of the presence of commensal microbiota, poses a threat of autoimmunity. The Rockefeller University Press 2010-10-25 /pmc/articles/PMC2964571/ /pubmed/20921284 http://dx.doi.org/10.1084/jem.20101235 Text en © 2010 Chinen et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Brief Definitive Report Chinen, Takatoshi Volchkov, Pavel Y. Chervonsky, Alexander V. Rudensky, Alexander Y. A critical role for regulatory T cell–mediated control of inflammation in the absence of commensal microbiota |
title | A critical role for regulatory T cell–mediated control of inflammation in the absence of commensal microbiota |
title_full | A critical role for regulatory T cell–mediated control of inflammation in the absence of commensal microbiota |
title_fullStr | A critical role for regulatory T cell–mediated control of inflammation in the absence of commensal microbiota |
title_full_unstemmed | A critical role for regulatory T cell–mediated control of inflammation in the absence of commensal microbiota |
title_short | A critical role for regulatory T cell–mediated control of inflammation in the absence of commensal microbiota |
title_sort | critical role for regulatory t cell–mediated control of inflammation in the absence of commensal microbiota |
topic | Brief Definitive Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2964571/ https://www.ncbi.nlm.nih.gov/pubmed/20921284 http://dx.doi.org/10.1084/jem.20101235 |
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