A critical role for regulatory T cell-mediated control of inflammation in the absence of commensal microbiota Journal Article
| Authors: | Chinen, T.; Volchkov, P. Y.; Chervonsky, A. V.; Rudensky, A. Y. |
| Article Title: | A critical role for regulatory T cell-mediated control of inflammation in the absence of commensal microbiota |
| Abstract: | 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. © 2010 Chinen et al. |
| Keywords: | controlled study; myeloproliferative disorder; nonhuman; animal cell; mouse; animals; mice; mice, knockout; animal tissue; animal experiment; inflammation; regulatory t lymphocyte; disease severity; cellular immunity; t-lymphocytes, regulatory; pancreatitis; enteritis; immunity, innate; adaptive immunity; t cell depletion; autoimmune disease; intestine, small; lymphocyte depletion; lymphocyte function; major histocompatibility complex restriction; autoimmune lymphoproliferative syndrome; commensal; systemic inflammatory response syndrome; bacteria; germ-free life |
| Journal Title: | Journal of Experimental Medicine |
| Volume: | 207 |
| Issue: | 11 |
| ISSN: | 0022-1007 |
| Publisher: | Rockefeller University Press |
| Date Published: | 2010-10-25 |
| Start Page: | 2323 |
| End Page: | 2330 |
| Language: | English |
| DOI: | 10.1084/jem.20101235 |
| PUBMED: | 20921284 |
| PROVIDER: | scopus |
| PMCID: | PMC2964571 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 2" - "Export Date: 20 April 2011" - "CODEN: JEMEA" - "Source: Scopus" |
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