Extrathymically generated regulatory T cells control mucosal T H 2 inflammation

Steven Z. Josefowicz, Rachel E. Niec, Hye Young Kim, Piper Treuting, Takatoshi Chinen, Ye Zheng, Dale T. Umetsu, Alexander Y. Rudensky

Research output: Contribution to journalArticle

492 Citations (Scopus)

Abstract

A balance between pro-and anti-inflammatory mechanisms at mucosal interfaces, which are sites of constitutive exposure to microbes and non-microbial foreign substances, allows for efficient protection against pathogens yet prevents adverse inflammatory responses associated with allergy, asthma and intestinal inflammation. Regulatory T (T reg) cells prevent systemic and tissue-specific autoimmunity and inflammatory lesions at mucosal interfaces. These cells are generated in the thymus (tT reg cells) and in the periphery (induced (i)T reg cells), and their dual origin implies a division of labour between tT reg and iT reg cells in immune homeostasis. Here we show that a highly selective blockage in differentiation of iT reg cells in mice did not lead to unprovoked multi-organ autoimmunity, exacerbation of induced tissue-specific autoimmune pathology, or increased pro-inflammatory responses of T helper 1 (T H 1) and T H 17 cells. However, mice deficient in iT reg cells spontaneously developed pronounced T H 2-type pathologies at mucosal sites-in the gastrointestinal tract and lungs-with hallmarks of allergic inflammation and asthma. Furthermore, iT reg-cell deficiency altered gut microbial communities. These results suggest that whereas T reg cells generated in the thymus appear sufficient for control of systemic and tissue-specific autoimmunity, extrathymic differentiation of T reg cells affects commensal microbiota composition and serves a distinct, essential function in restraint of allergic-type inflammation at mucosal interfaces.

Original languageEnglish
Pages (from-to)395-399
Number of pages5
JournalNature
Volume482
Issue number7385
DOIs
Publication statusPublished - Feb 16 2012

All Science Journal Classification (ASJC) codes

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    Josefowicz, S. Z., Niec, R. E., Kim, H. Y., Treuting, P., Chinen, T., Zheng, Y., Umetsu, D. T., & Rudensky, A. Y. (2012). Extrathymically generated regulatory T cells control mucosal T H 2 inflammation. Nature, 482(7385), 395-399. https://doi.org/10.1038/nature10772