Cited by 393T-cell and B-cell ImmunologyPsoriasis: Treatment and PathogenesisGenomics and Chromatin Dynamics

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Gata-3 Induces T Helper Cell Type 2 (Th2) Cytokine Expression and Chromatin Remodeling in Committed Th1 Cells

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Lee, Hyun Jun, Takemoto, Naofumi, Kurata, Hirokazu, Kamogawa, Yumiko, Miyatake, Shoichiro, O'Garra, Anne, Arai, Naoko·2000·The Journal of Experimental Medicine

DOI 10.1084/jem.192.1.105PMC PMC1887713

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Abstract

Committed T helper type 1 (Th1) and Th2 effector cells, resulting from chronic antigenic stimulation in interleukin (IL)-12 and IL-4, are implicated in the pathology of autoimmune and allergic diseases. Committed Th1 cells cannot be induced to change their cytokine profiles in response to antigenic stimulation and Th2 cytokine–inducing conditions. Here, we report that ectopic expression of GATA-3 induced Th2-specific cytokine expression not only in developing Th1 cells but also in otherwise irreversibly committed Th1 cells and a Th1 clone, HDK1. Moreover, cAMP, an inhibitor of cytokine production by Th1 cells, markedly augmented Th2 cytokine production in GATA-3–expressing Th1 cells. Ectopic expression of GATA-3 in developing Th1 cells, but not in Th1 clone HDK1, induced endogenous GATA-3, suggesting an autoregulatory mechanism for maintenance of GATA-3 expression in Th2 cells. Structure–function analyses of GATA-3 revealed that the NH2-terminal transactivation domain and the COOH-terminal zinc finger domain of GATA-3 were critical, whereas the NH2-terminal zinc finger domain was dispensable for the induction of IL-4. Both zinc fingers, however, were required for IL-5 induction. A Th2-specific DNaseI-hypersensitive site of the IL-4 locus was detected in GATA-3–expressing Th1 cells. Thus, GATA-3 can change the phenotype of committed Th1 cells, previously considered to be irreversible.

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Authors: Lee, H. J., Takemoto, N., Kurata, H., Kamogawa, Y., Miyatake, S., O'Garra, A., & Arai, N.
Affiliations: aDepartment of Immunology, DNAX Research Institute, Palo Alto, California 94304-1104
Institute of Medical Science, The University of Tokyo (JP)
ORCID: Lee, Hyun Jun
Kamogawa, Yumiko
Miyatake, Shoichiro
Venue: The Journal of Experimental Medicine
Publisher: Rockefeller University Press
Published: 2000-07-03
Volume: 192
Issue: 1
Pages: 105-116
ISSN: 0022-1007 (ISSN-L)
1540-9538
DOI: 10.1084/jem.192.1.105
PMC: PMC1887713
OpenAlex: W2119767265
Cited by: 393
References: 72
Citations by year: 2026: 4 · 2025: 5 · 2024: 8 · 2023: 5 · 2022: 1 · 2021: 9 · 2020: 7 · 2019: 4 · 2018: 11 · 2017: 7 · 2016: 13 · 2015: 8 · 2014: 22 · 2013: 13 · 2012: 9
FWCI: 10.63
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: cc-by-nc-sa
Locations: The Journal of Experimental Medicine (publishedVersion)
PubMed Central (publishedVersion, cc-by-nc-sa)
PubMed (publishedVersion)
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 › Genomics and Chromatin Dynamics
Keywords: GATA3, Th1 cells, Th2 cytokines, IL-4, IL-5, chromatin remodeling, DNase I hypersensitive sites, cyclic AMP, zinc finger, transactivation domain, T helper cell differentiation, cytokine gene expression
MeSH terms: Animals, Cells, Cultured, Chromatin, DNA-Binding Proteins, Gene Expression Regulation, Genetic Vectors, Interferon-gamma, Mice, Inbred BALB C, Moloney murine leukemia virus, Recombinant Proteins, Transfection, CD4-Positive T-Lymphocytes, Trans-Activators, Interleukin-4, Interleukin-5, Cytokines, Zinc Fingers, Th1 Cells, Th2 Cells, GATA3 Transcription Factor, Mice

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Gata-3 Induces T Helper Cell Type 2 (Th2) Cytokine Expression and Chromatin Remodeling in Committed Th1 Cells

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