The transcription factor t-bet controls regulatory t cell homeostasis and function during type 1 inflammation

ABSTRACT Several subsets of Foxp3+ regulatory T cells (Treg cells) work in concert to maintain immune homeostasis. However, the molecular bases underlying the phenotypic and functional

diversity of Treg cells remain obscure. We show that in response to interferon-γ, Foxp3+ Treg cells upregulated the T helper type 1 (TH1)-specifying transcription factor T-bet. T-bet

promoted expression of the chemokine receptor CXCR3 on Treg cells, and T-bet+ Treg cells accumulated at sites of TH1 cell–mediated inflammation. Furthermore, T-bet expression was required

for the homeostasis and function of Treg cells during type 1 inflammation. Thus, in a subset of CD4+ T cells, the activities of the transcription factors Foxp3 and T-bet are overlaid, which

results in Treg cells with unique homeostatic and migratory properties optimized for the suppression of TH1 responses _in vivo_. Access through your institution Buy or subscribe This is a

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OF TH1-LIKE REGULATORY T CELLS CONTROLS ANTIVIRAL RESPONSES Article 16 March 2023 THE REGULATION AND DIFFERENTIATION OF REGULATORY T CELLS AND THEIR DYSFUNCTION IN AUTOIMMUNE DISEASES

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Download references ACKNOWLEDGEMENTS We thank A. Weinmann (University of Washington) for _Tbx21__−/−_ mice; A. Rudensky (University of Washington) for _Foxp3_GFP mice; S. Ziegler (Benaroya

Research Institute) for mice with overexpression of thymic stromal lymphopoietin and for _Il4__−/−_ and _Stat6__−/−_ mice; M. Krishna-Kaja (University of Washington) for splenocytes from

_Stat1__−/−_ mice; L. Thompson and K. Smigiel for technical assistance; G. Debes, K. Klonowski and J. Hamerman for comments on the manuscript; and M. Warren for administrative assistance.

Supported by the US National Institutes of Health (DK072295, AI067750 and AI069889 to D.J.C.), the US Department of Defense (USAMRAA W81XWH-07-0246 to D.J.C.), the Burroughs-Wellcome Fund

(K.B.U.) and the Department of Immunology at the University of Washington Medical School (T32-CA009537 to M.A.K.). AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Benaroya Research Institute,

Seattle, Washington, USA Meghan A Koch, Nikole R Perdue, Justin R Killebrew & Daniel J Campbell * Department of Immunology, University of Washington School of Medicine, Seattle,

Washington, USA Meghan A Koch, Justin R Killebrew & Daniel J Campbell * Department of Pediatrics, University of Washington School of Medicine, Seattle, Washington, USA Glady's

Tucker-Heard & Kevin B Urdahl Authors * Meghan A Koch View author publications You can also search for this author inPubMed Google Scholar * Glady's Tucker-Heard View author

publications You can also search for this author inPubMed Google Scholar * Nikole R Perdue View author publications You can also search for this author inPubMed Google Scholar * Justin R

Killebrew View author publications You can also search for this author inPubMed Google Scholar * Kevin B Urdahl View author publications You can also search for this author inPubMed Google

Scholar * Daniel J Campbell View author publications You can also search for this author inPubMed Google Scholar CONTRIBUTIONS M.A.K., K.B.U. and D.J.C. designed the study, analyzed data and

wrote the manuscript, and M.A.K. and D.J.C. did experiments with assistance from N.R.P., J.R.K. and G.T-H. CORRESPONDING AUTHOR Correspondence to Daniel J Campbell. SUPPLEMENTARY

INFORMATION SUPPLEMENTARY TEXT AND FIGURES Supplementary Figures 1–11 and Supplementary Table 1 (PDF 590 kb) RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS

ARTICLE Koch, M., Tucker-Heard, G., Perdue, N. _et al._ The transcription factor T-bet controls regulatory T cell homeostasis and function during type 1 inflammation. _Nat Immunol_ 10,

595–602 (2009). https://doi.org/10.1038/ni.1731 Download citation * Received: 17 February 2009 * Accepted: 26 March 2009 * Published: 03 May 2009 * Issue Date: June 2009 * DOI:

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