A critical role for regulatory T cell-mediated control of inflammation in the absence of commensal microbiota

Takatoshi Chinen, Pavel Y. Volchkov, Alexander V. Chervonsky, Alexander Y. Rudensky

Research output: Contribution to journalArticlepeer-review

84 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2323-2330
Number of pages8
JournalJournal of Experimental Medicine
Volume207
Issue number11
DOIs
Publication statusPublished - Oct 25 2010
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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