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

Abstract

Several subsets of Foxp3 ⁺ regulatory T (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 1 (T _H1)-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 _H1-mediated inflammation. Furthermore, T-bet expression was required for the homeostasis and function of T _reg cells during type-1 inflammation. Thus, within a subset of CD4 ⁺ T cells, the activities of Foxp3 and T-bet are overlaid, resulting in T _reg cells with unique homeostatic and migratory properties optimized for suppression of T _H1 responses in vivo.