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Transforming Growth Factor-β Signaling in Regulatory T Cells Controls T Helper-17 Cells and Tissue-Specific Immune Responses.

Abstract

Regulatory T cells (Treg cells) perform suppressive functions in disparate tissue environments and against many inflammatory insults, yet the tissue-enriched factor(s) that influence Treg cell phenotype and function remain largely unknown. We have shown a vital role for transforming growth factor-β (TGF-β) signals in safe-guarding specific Treg cell functions. TGF-β signals were dispensable for steady-state Treg cell homeostasis and for Treg cell suppression of T cell proliferation and T helper-1 (Th1) cell differentiation. However, Treg cells require TGF-β signals to appropriately dampen Th17 cells and regulate responses in the gastrointestinal tract. TGF-β signaling maintains CD103 expression, promotes expression of the colon-specific trafficking molecule GPR15, and inhibits expression of GPR174, a receptor for lysophosphatidylserine, on Treg cells, collectively supporting the accumulation and retention of Treg cells in the colon and control of colitogenic responses. Thus, we reveal an unrecognized function for TGF-β signaling as an upstream factor controlling Treg cell activity in specific tissue environments.

Authors+Show Affiliations

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Mucosal Immunology Section, OPCB, NIDCR, NIH, Bethesda, MD 20892, USA; Faculty of Biology, Medicine and Health and Manchester Collaborative Centre for Inflammation Research, University of Manchester, Manchester M13 9PT, UK. Electronic address: joanne.konkel@manchester.ac.uk.

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Mucosal Immunology Section, OPCB, NIDCR, NIH, Bethesda, MD 20892, USA.

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Mucosal Immunology Section, OPCB, NIDCR, NIH, Bethesda, MD 20892, USA.

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Mucosal Immunology Section, OPCB, NIDCR, NIH, Bethesda, MD 20892, USA.

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Faculty of Biology, Medicine and Health and Manchester Collaborative Centre for Inflammation Research, University of Manchester, Manchester M13 9PT, UK.

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Mucosal Immunology Section, OPCB, NIDCR, NIH, Bethesda, MD 20892, USA.

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Molecular Laboratory for Gene Therapy and Tooth Regeneration, Capital Medical University School of Basic Medical Sciences, 100050 Beijing, China.

Mucosal Immunology Section, OPCB, NIDCR, NIH, Bethesda, MD 20892, USA. Electronic address: wchen@mail.nih.gov.

Source

Immunity 46:4 2017 Apr 18 pg 660-674

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28423340