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

By M. Koch, G. Tucker-Heard, N. Perdue, J. Killebrew, K. Urdahl, D. Campbell. Nature Immunology, 2009

857 citations recorded by the source corpus.

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.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/8a16b597fee64730cb2b0634cbc043d5bd91925e

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Citations in the corpus

Molecular Mechanisms of Treg-Mediated T Cell Suppression (2012, background): “In this regard, it was shown that a Treg subset upregulated T-bet in response to IFN-γ, which was essential for the control of Th1-mediated inflammation (Koch et al., 2009) ).”
Regulatory T cells: how do they suppress immune responses? (2009, background): “tion factor T-bet, which increases in Tregs stimulated in a Th1 cytokine milieu, causing the subsequent up-regulation of C‐X‐C chemokine receptor 3, a T-bet-controlled chemokine receptor, leading to Treg recruitment to type 1 inflammation sites ( 74 ).”
The transcription factors Blimp-1 and IRF4 jointly control the differentiation and function of effector regulatory T cells (2011, background): “In an analogous manner, the transcription factors T-bet and STAT3 control the homeostasis and function of T reg cells during T H 1 and T H 17 inflammation, respectivel”
Peripheral CD4 T cell differentiation regulated by networks of cytokines and transcription factors (2010, background): “T-bet is found to be co-expressed with Foxp3 (128), and our unpublished data suggest GATA3 is expressed by Foxp3 cells.”
Development and maintenance of regulatory T cells. (2013, background): “Koch et al. (Koch et al., 2009) revealed that in Treg cells, delayed induction of IL12Rb2 after STAT1 activation helps ensure that Treg cells do not readily complete Th1 cell differentiation and lose their suppressive ability.”
Phenotypic and functional specialization of FOXP3+ regulatory T cells (2011, background): “Interestingly, T-bet is also expressed by a subset of T Reg cells, and is required for T Reg cell homeostasis and function during polarized T H 1-type inflammatory response”
Cross-regulation of Signaling and Immune Responses by IFN-γ and STAT1 (2009, background): “Two elegant studies suggest that, similar to effector T cells, Treg cells undergo polarization into specialized phenotypes and that factors important for effector T cell development may also play a critical role in Treg cell polarization (Koch et al., 2009; Zheng et al., 2009).”