title: GATA3 controls Foxp3⁺ regulatory T cell fate during inflammation in mice.
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.affiliation: Mucosal Immunology Unit, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Wohlfert
authors.forename: John R
authors.initials: JR
authors.lastname: Grainger
authors.forename: Nicolas
authors.initials: N
authors.lastname: Bouladoux
authors.forename: Joanne E
authors.initials: JE
authors.lastname: Konkel
authors.forename: Guillaume
authors.initials: G
authors.lastname: Oldenhove
authors.forename: Carolina Hager
authors.initials: CH
authors.lastname: Ribeiro
authors.forename: Jason A
authors.initials: JA
authors.lastname: Hall
authors.forename: Ryoji
authors.initials: R
authors.lastname: Yagi
authors.forename: Shruti
authors.initials: S
authors.lastname: Naik
authors.forename: Ravikiran
authors.initials: R
authors.lastname: Bhairavabhotla
authors.forename: William E
authors.initials: WE
authors.lastname: Paul
authors.forename: Remy
authors.initials: R
authors.lastname: Bosselut
authors.forename: Gang
authors.initials: G
authors.lastname: Wei
authors.forename: Keji
authors.initials: K
authors.lastname: Zhao
authors.forename: Mohamed
authors.initials: M
authors.lastname: Oukka
authors.forename: Jinfang
authors.initials: J
authors.lastname: Zhu
authors.forename: Yasmine
authors.initials: Y
authors.lastname: Belkaid
mesh_terms: D000818:Animals; D016207:Cytokines / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D005260:Female; D051858:Forkhead Transcription Factors / Q000276:immunology*; D050990:GATA3 Transcription Factor / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D041981:Gastrointestinal Tract / Q000276:immunology / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D012867:Skin / Q000276:immunology / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation
chemical_list: D016207:Cytokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; C494748:Gata3 protein, mouse; D011948:Receptors, Antigen, T-Cell