GATA3 controls Foxp3+ regulatory T cell fate during inflammation in mice
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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.
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Tregs can develop T-bet expression and transform into Th1-like Tregs, which can then produce IFN-γ to help the immune system target tumor cells.
“Tregs can develop T-bet expression and transform into Th1-like Tregs, which can then produce IFN-γ to help the immune system target tumor cells [25].”
From Potential anti-tumor effects of regulatory T cells in the tumor microenvironment: a review (2024) · cites this paper as [25]
An increasing list of transcription factors, including IRF4, STAT3, T-bet, GATA3, Bcl-6, and Blimp-1, regulate both effector T cell function and regulatory T cell function.
“an increasing list of transcription factors now shown to regulate both effector T cell function and regulatory T cell function, including IRF4, STAT3, T-bet, GATA3, Bcl-6, and Blimp-1 [98–105].”
From Hypoxia and hypoxia-inducible factors as regulators of T cell development, differentiation, and function (2013) · cites this paper as [105]
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- Authors
- Wohlfert, E. A., Grainger, J. R., Bouladoux, N., Konkel, J. E., Oldenhove, G., Ribeiro, C. H., Hall, J. A., Yagi, R., Naik, S., Bhairavabhotla, R., Paul, W. E., Bosselut, R., Wei, G., Zhao, K., Oukka, M., Zhu, J., & Belkaid, Y.
- Affiliations
- National Institutes of Health (US)
- University of Pennsylvania (US)
- University of Washington (US)
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 2011-11-01
- Volume
- 121
- Issue
- 11
- Pages
- 4503-4515
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC3204837
- OpenAlex
- W2143417567
- Cited by
- 556
- References
- 85
- Citations by year
- 2026: 29 · 2025: 27 · 2024: 37 · 2023: 48 · 2022: 44 · 2021: 41 · 2020: 35 · 2019: 40 · 2018: 42 · 2017: 54 · 2016: 34 · 2015: 40 · 2014: 29 · 2013: 34 · 2012: 20
- FWCI
- 11.87
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Clinical Investigation (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion)
- Americanae (AECID Library) (submittedVersion, other-oa)
- Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, other-oa)
- Funders
- Crohn's and Colitis Foundation of America
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases
- Crohn's and Colitis Foundation
- National Institutes of Health
- National Cancer Institute
- National Institute of Allergy and Infectious Diseases (ZIAAI001169)
- NHLBI Division of Intramural Research
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Life Sciences › Immunology and Microbiology › Immunology › IL-33, ST2, and ILC Pathways
- Keywords
- GATA3, Foxp3, regulatory T cells, inflammation, gastrointestinal tract, skin, effector cytokines, T cell receptor stimulation, IL-2 stimulation, immune homeostasis
- MeSH terms
- Animals, Female, Humans, Inflammation, Male, Mice, Inbred C57BL, Mice, Transgenic, Receptors, Antigen, T-Cell, Skin, Up-Regulation, Cytokines, Mice, Knockout, Gastrointestinal Tract, T-Lymphocytes, Regulatory, GATA3 Transcription Factor, Mice, Forkhead Transcription Factors
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