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PMID: 21511185 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Interleukin-10 signaling in regulatory T cells is required for suppression of Th17 cell-mediated inflammation.

Immunity ·Vol. 34 ·No. 4 ·2011-04-22 ·Pages 566-78

Chaudhry A, Samstein RM, Treuting P, Liang Y, Pils MC, Heinrich JM, Jack RS, Wunderlich FT, Brüning JC, Müller W, Rudensky AY

Abstract

Effector CD4+ T cell subsets, whose differentiation is facilitated by distinct cytokine cues, amplify the corresponding type of inflammatory response. Regulatory T (Treg) cells integrate environmental cues to suppress particular types of inflammation. In this regard, STAT3, a transcription factor essential for T helper 17 (Th17) cell differentiation, is necessary for Treg cell-mediated control of Th17 cell responses. Here, we showed that anti-inflammatory interleukin-10 (IL-10), and not proinflammatory IL-6 and IL-23 cytokine signaling, endowed Treg cells with the ability to suppress pathogenic Th17 cell responses. Ablation of the IL-10 receptor in Treg cells resulted in selective dysregulation of Th17 cell responses and colitis similar to that observed in mice harboring STAT3-deficient Treg cells. Thus, Treg cells limit Th17 cell inflammation by serving as principal amplifiers of negative regulatory circuits operating in immune effector cells.

MeSH Terms
Animals Cell Lineage Colitis/immunology,pathology Interleukin-10/immunology,metabolism Mice Mice, Knockout Phosphorylation Receptors, Interleukin-10/deficiency,immunology STAT3 Transcription Factor/immunology,metabolism Signal Transduction T-Lymphocytes, Regulatory/cytology,immunology Th17 Cells/immunology
Chemicals
IL10 protein, mouse Receptors, Interleukin-10 STAT3 Transcription Factor Stat3 protein, mouse Interleukin-10
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Chaudhry Ashutosh
Howard Hughes Medical Institute and Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
Samstein Robert M
Treuting Piper
Liang Yuqiong
Pils Marina C
Heinrich Jan-Michael
Jack Robert S
Wunderlich F Thomas
Brüning Jens C
Müller Werner
Rudensky Alexander Y
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Article Info
Journal
Immunity
Abbr.
Immunity
ISSN
1097-4180
DOI
10.1016/j.immuni.2011.03.018
Published
2011-04-22
Pages
566-78
Language
English
Region
United States
NLM ID
9432918
PMCID
PMC3088485
Subset
IM
Grants
NIGMS NIH HHS · GM07739 · United States
Howard Hughes Medical Institute · United States
NIAID NIH HHS · R37 AI034206 · United States
NIDDK NIH HHS · F30 DK091968 · United States
NIGMS NIH HHS · T32 GM007739 · United States
Corrections
CommentIn
PMID: 21511180
External Links
PubMed source DOI: 10.1016/j.immuni.2011.03.018 PMC Full Text View journal details
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