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

Koch, Meghan A; Tucker-Heard, Glady's; Perdue, Nikole R; Killebrew, Justin R; Urdahl, Kevin B; Campbell, Daniel J

doi:10.1038/ni.1731

Cited by 1,258T-cell and B-cell ImmunologyPsoriasis: Treatment and PathogenesisIL-33, ST2, and ILC Pathways

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

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Koch, Meghan A, Tucker-Heard, Glady's, Perdue, Nikole R, Killebrew, Justin R, Urdahl, Kevin B, Campbell, Daniel J·2009·Nature Immunology

DOI 10.1038/ni.1731PMC PMC2712126

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Abstract

Several subsets of Foxp3(+) regulatory T cells (T(reg) cells) work in concert to maintain immune homeostasis. However, the molecular bases underlying the phenotypic and functional diversity of T(reg) cells remain obscure. We show that in response to interferon-gamma, Foxp3(+) T(reg) cells upregulated the T helper type 1 (T(H)1)-specifying transcription factor T-bet. T-bet promoted expression of the chemokine receptor CXCR3 on T(reg) cells, and T-bet(+) T(reg) cells accumulated at sites of T(H)1 cell-mediated inflammation. Furthermore, T-bet expression was required for the homeostasis and function of T(reg) 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 T(reg) cells with unique homeostatic and migratory properties optimized for the suppression of T(H)1 responses in vivo.

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An increasing list of transcription factors, including IRF4, STAT3, T-bet, GATA3, Bcl-6, and Blimp-1, regulate both effector T cell function and regulatory T cell function.
“an increasing list of transcription factors now shown to regulate both effector T cell function and regulatory T cell function, including IRF4, STAT3, T-bet, GATA3, Bcl-6, and Blimp-1 [98–105].”
From Hypoxia and hypoxia-inducible factors as regulators of T cell development, differentiation, and function (2013) · cites this paper as [100]

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Authors: Koch, M. A., Tucker-Heard, G., Perdue, N. R., Killebrew, J. R., Urdahl, K. B., & Campbell, D. J.
Affiliations: University of Washington (US)
Benaroya Research Institute (US)
Corresponding author: Campbell, Daniel J
ORCID: Koch, Meghan A
Urdahl, Kevin B
Campbell, Daniel J
Venue: Nature Immunology
Publisher: Springer Science and Business Media LLC
Published: 2009-05-03
Volume: 10
Issue: 6
Pages: 595-602
ISSN: 1529-2908 (ISSN-L)
1529-2916
DOI: 10.1038/ni.1731
PMC: PMC2712126
OpenAlex: W1987735044
Cited by: 1,258
References: 52
Citations by year: 2026: 38 · 2025: 46 · 2024: 57 · 2023: 58 · 2022: 61 · 2021: 68 · 2020: 74 · 2019: 76 · 2018: 71 · 2017: 82 · 2016: 72 · 2015: 95 · 2014: 86 · 2013: 93 · 2012: 91
FWCI: 39.90
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Nature Immunology (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: Wellcome Trust
National Cancer Institute (T32CA009537)
National Institute of Allergy and Infectious Diseases (AI067750, R56AI067750, AI069889, R01AI067750, R21AI069889)
National Institute of Diabetes and Digestive and Kidney Diseases (DK072295, R01DK072295)
Topics: Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
Life Sciences › Immunology and Microbiology › Immunology › IL-33, ST2, and ILC Pathways
Keywords: T-bet, regulatory T cells, Foxp3, type 1 inflammation, interferon-gamma, CXCR3, immune homeostasis, Treg cell migration, immunosuppression
MeSH terms: T-bet Transcription Factor, Animals, Cell Differentiation, Cell Movement, Cells, Cultured, Gene Expression Regulation, Homeostasis, Inflammation, Interferon-gamma, Lymphocyte Activation, Mice, Inbred BALB C, Mice, Inbred C57BL, Up-Regulation, Mice, Knockout, Th1 Cells, T-Box Domain Proteins, Cell Proliferation, T-Lymphocytes, Regulatory, Mice, Forkhead Transcription Factors, Receptors, CXCR3

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

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