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T cell factor 1 initiates the T helper type 2 fate by inducing the transcription factor GATA-3 and repressing interferon-γ
Open accessAbstract
The differentiation of activated CD4(+) T cells into the T helper type 1 (T(H)1) or T(H)2 fate is regulated by cytokines and the transcription factors T-bet and GATA-3. Whereas interleukin 12 (IL-12) produced by antigen-presenting cells initiates the T(H)1 fate, signals that initiate the T(H)2 fate are not completely characterized. Here we show that early GATA-3 expression, required for T(H)2 differentiation, was induced by T cell factor 1 (TCF-1) and its cofactor beta-catenin, mainly from the proximal Gata3 promoter upstream of exon 1b. This activity was induced after T cell antigen receptor (TCR) stimulation and was independent of IL-4 receptor signaling through the transcription factor STAT6. Furthermore, TCF-1 blocked T(H)1 fate by negatively regulating interferon-gamma (IFN-gamma) expression independently of beta-catenin. Thus, TCF-1 initiates T(H)2 differentiation of activated CD4(+) T cells by promoting GATA-3 expression and suppressing IFN-gamma expression.
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“In fact, GATA3 expression can also be induced by T cell receptor (TCR) signaling [41] and other pathways, such as Notch [42] and WNT signaling [43].”
From Picroside II Attenuates Airway Inflammation by Downregulating the Transcription Factor GATA3 and Th2-Related Cytokines in a Mouse Model of HDM-Induced Allergic Asthma (2016) · cites this paper as [43]
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Metadata
- Authors
- Yu, Q., Sharma, A., Oh, S. Y., Moon, H.-G., Hossain, M. Z., Salay, T. M., Leeds, K. E., Du, H., Wu, B., Waterman, M. L., Zhu, Z., & Sen, J. M.
- Affiliations
- National Institutes of Health (US)
- Johns Hopkins University (US)
- University of California, Irvine (US)
- Corresponding author
- Sen, Jyoti Misra
- ORCID
- Venue
- Nature Immunology
- Published
- 2009-08-02
- Volume
- 10
- Issue
- 9
- Pages
- 992-999
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- PMC
- PMC2824257
- OpenAlex
- W2007359758
- Cited by
- 208
- References
- 50
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 11 · 2023: 4 · 2022: 10 · 2021: 16 · 2020: 12 · 2019: 11 · 2018: 10 · 2017: 12 · 2016: 16 · 2015: 20 · 2014: 13 · 2013: 14 · 2012: 15
- FWCI
- 7.05
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Canadian Institute for Theoretical Astrophysics
- National Institutes of Health
- National Institute on Aging (Z01AG000772)
- 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 › Wnt/β-catenin signaling in development and cancer
- Keywords
- TCF1, GATA3, T cell receptor signaling, β-catenin, CD4+ T cell polarization, STAT6, T-bet
- MeSH terms
- Animals, Cell Differentiation, Interferon-gamma, Mice, Inbred C57BL, Promoter Regions, Genetic, Receptors, Antigen, T-Cell, Interleukin-4, Th2 Cells, Interleukin-12, GATA3 Transcription Factor, beta Catenin, Mice, T Cell Transcription Factor 1, Receptors, Notch
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