Extrathymically generated regulatory T cells control mucosal T(H)2 inflammation Journal Article

Authors: Josefowicz, S. Z.; Niec, R. E.; Kim, H. Y.; Treuting, P.; Chinen, T.; Zheng, Y.; Umetsu, D. T.; Rudensky, A. Y.
Article Title: Extrathymically generated regulatory T cells control mucosal T(H)2 inflammation
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. © 2012 Macmillan Publishers Limited. All rights reserved.
Keywords: controlled study; protein expression; nonhuman; transcription factor foxp3; forkhead transcription factors; animal cell; mouse; animals; mice; mus; disease association; transcription factor gata 3; allergy; interleukin 13; interleukin 4; interleukin 5; animal experiment; animal model; inflammation; cell differentiation; pathology; lymphocyte differentiation; regulatory t lymphocyte; th2 cell; immune response; gamma interferon; thymus; t-lymphocytes, regulatory; thymus gland; cd4+ t lymphocyte; lung; organ specificity; enteritis; cytokine production; effector cell; autoimmunity; asthma; rodent; th1 cell; intestine flora; homeostasis; cre recombinase; disease exacerbation; intestines; cell organelle; stomach; enhancer elements, genetic; th2 cells; myelin oligodendrocyte glycoprotein; protection; biochemical composition; microbial community; pathogen; immunity, mucosal; mucosal immunity
Journal Title: Nature
Volume: 482
Issue: 7385
ISSN: 0028-0836
Publisher: Nature Publishing Group  
Date Published: 2012-02-08
Start Page: 395
End Page: 399
Language: English
DOI: 10.1038/nature10772
PUBMED: 22318520
PROVIDER: scopus
PMCID: PMC3485072
Notes: --- - "Cited By (since 1996): 2" - "Export Date: 7 May 2012" - "CODEN: NATUA" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Alexander Rudensky
    102 Rudensky
  2. Takatoshi Chinen
    6 Chinen
  3. Rachel E Niec
    8 Niec