An Essential Role of the Transcription Factor GATA-3 for the Function of Regulatory T Cells
Open accessAbstract
Forkhead Box P3 (Foxp3)-expressing regulatory T (Treg) cells are central to maintaining self-tolerance and immune homeostasis. How Treg cell function and Foxp3 expression are regulated is an important question under intensive investigation. Here, we have demonstrated an essential role for the transcription factor GATA-3, a previously recognized Th2 cell master regulator, in controlling Treg cell function. Treg cell-specific GATA-3 deletion led to a spontaneous inflammatory disorder in mice. GATA-3-null Treg cells were defective in peripheral homeostasis and suppressive function, gained Th17 cell phenotypes, and expressed reduced amounts of Foxp3. In addition, GATA-3 controlled Foxp3 expression by binding to and promoting the activity of cis-acting elements of Foxp3. Furthermore, the combined function of GATA-3 and Foxp3 was essential for Foxp3 expression. These findings provide insights into immune regulatory mechanisms and uncover a critical function of GATA-3 in Treg cells and immune tolerance.
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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 [104]
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References 48 · Cited by 461
- Authors
- Wang, Y., Su, M. A., & Wan, Y. Y.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Wan, Yisong Y.
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2011-09
- Volume
- 35
- Issue
- 3
- Pages
- 337-348
- ISSN
- 1074-7613 (ISSN-L)
- PMC
- PMC3182399
- OpenAlex
- W2076841462
- Cited by
- 461
- References
- 48
- Citations by year
- 2026: 17 · 2025: 30 · 2024: 32 · 2023: 38 · 2022: 33 · 2021: 26 · 2020: 28 · 2019: 39 · 2018: 27 · 2017: 39 · 2016: 19 · 2015: 37 · 2014: 31 · 2013: 30 · 2012: 33
- FWCI
- 13.62
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 721 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UNC Libraries
- Funders
- Lupus Research Institute
- Yale University
- Lupus Research Alliance
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases (R00AI072956, K08AI076429, R01AI097392, K99AI072956)
- 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 › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Keywords
- GATA3, regulatory T cells, Foxp3, transcriptional regulation, Th17 cells, Treg suppressive function, immune tolerance, self-tolerance
- MeSH terms
- Animals, Cells, Cultured, Flow Cytometry, Gene Expression Regulation, Homeostasis, Immune Tolerance, Mice, Inbred C57BL, Protein Binding, Down-Regulation, Cytokines, Mice, Knockout, Cell Proliferation, T-Lymphocytes, Regulatory, GATA3 Transcription Factor, Mice, Forkhead Transcription Factors
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