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

MA Koch, G Tucker-Heard, NR Perdue… - Nature …, 2009 - nature.com
MA Koch, G Tucker-Heard, NR Perdue, JR Killebrew, KB Urdahl, DJ Campbell
Nature immunology, 2009nature.com
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-γ,
Foxp3+ T reg cells upregulated the T helper type 1 (TH 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 TH 1 cell–mediated inflammation. Furthermore, T-bet …
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-γ, 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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