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GATA3 controls Foxp3+ regulatory T cell fate during inflammation in mice
Elizabeth A. Wohlfert, … , Jinfang Zhu, Yasmine Belkaid
Elizabeth A. Wohlfert, … , Jinfang Zhu, Yasmine Belkaid
Published October 3, 2011
Citation Information: J Clin Invest. 2011;121(11):4503-4515. https://doi.org/10.1172/JCI57456.
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Research Article Immunology

GATA3 controls Foxp3+ regulatory T cell fate during inflammation in mice

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Abstract

Tregs not only keep immune responses to autoantigens in check, but also restrain those directed toward pathogens and the commensal microbiota. Control of peripheral immune homeostasis by Tregs relies on their capacity to accumulate at inflamed sites and appropriately adapt to their local environment. To date, the factors involved in the control of these aspects of Treg physiology remain poorly understood. Here, we show that the canonical Th2 transcription factor GATA3 is selectively expressed in Tregs residing in barrier sites including the gastrointestinal tract and the skin. GATA3 expression in both murine and human Tregs was induced upon TCR and IL-2 stimulation. Although GATA3 was not required to sustain Treg homeostasis and function at steady state, GATA3 played a cardinal role in Treg physiology during inflammation. Indeed, the intrinsic expression of GATA3 by Tregs was required for their ability to accumulate at inflamed sites and to maintain high levels of Foxp3 expression in various polarized or inflammatory settings. Furthermore, our data indicate that GATA3 limits Treg polarization toward an effector T cell phenotype and acquisition of effector cytokines in inflamed tissues. Overall, our work reveals what we believe to be a new facet in the complex role of GATA3 in T cells and highlights what may be a fundamental role in controlling Treg physiology during inflammation.

Authors

Elizabeth A. Wohlfert, John R. Grainger, Nicolas Bouladoux, Joanne E. Konkel, Guillaume Oldenhove, Carolina Hager Ribeiro, Jason A. Hall, Ryoji Yagi, Shruti Naik, Ravikiran Bhairavabhotla, William E. Paul, Remy Bosselut, Gang Wei, Keji Zhao, Mohamed Oukka, Jinfang Zhu, Yasmine Belkaid

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Figure 6

GATA3-deficient Tregs do not protect from colitis.

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GATA3-deficient Tregs do not protect from colitis.
(A) Rag-KO mice recei...
(A) Rag-KO mice received either CD4+CD45RBhiCD45.1+ alone (white squares) or in combination with CD4+CD25brightCD45.2+ littermate Gata3f/f Tregs (black circles) or Gata3f/f-OX40Cre Tregs (black circles). **P < 0.001. Mice were weighed weekly and (B) tissue samples taken for H&E staining. Original magnification, ×20. (C) Graphical representation of histological score of mice; see Methods for scoring. Each symbol represents 1 mouse, and crossbars depict the mean of 3–4 mice analyzed. *P < 0.0114, Gata3f/f Treg compared with Gata3f/f-OX40Cre Tregs; **P < 0.0089, CD45RBhi compared with Gata3f/f Tregs. (D and E) Gata3f/f-OX40Cre Tregs were harvested from the SILp and stained for congenic markers CD45.1, CD45.2, CD4, TCR-β, and Foxp3; graph depicts percentage of Foxp3+CD4+ cells from colons of recipient mice. ***P < 0.0003. Numbers in quadrants refer to the percentage of each subset. Data shown are representative of 3 independent experiments with similar results. Data are presented as mean ± SEM.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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