Cited by 396T-cell and B-cell ImmunologyDevelopmental Biology and Gene RegulationPsoriasis: Treatment and Pathogenesis

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Direct Regulation of Gata3 Expression Determines the T Helper Differentiation Potential of Notch

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Amsen, Derk, Antov, Andrey, Jankovic, Dragana, Sher, Alan, Radtke, Freddy, Souabni, Abdallah, Busslinger, Meinrad, McCright, Brent, Gridley, Thomas, Flavell, Richard A.·2007·Immunity

DOI 10.1016/j.immuni.2007.05.021PMC PMC2062505

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Abstract

CD4(+) T helper cells differentiate into T helper 1 (Th1) or Th2 effector lineages, which orchestrate immunity to different types of microbes. Both Th1 and Th2 differentiation can be induced by Notch, but what dictates which of these programs is activated in response to Notch is not known. By using T cell-specific gene ablation of the Notch effector RBP-J or the Notch1 and 2 receptors, we showed here that Notch was required on CD4(+) T cells for physiological Th2 responses to parasite antigens. GATA-3 was necessary for Notch-induced Th2 differentiation, and we identified an upstream Gata3 promoter as a direct target for Notch signaling. Moreover, absence of GATA-3 turned Notch from a Th2 inducer into a powerful inducer of Th1 differentiation. Therefore, Gata3 is a critical element determining inductive Th2 differentiation and limiting Th1 differentiation by Notch.

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Authors: Amsen, D., Antov, A., Jankovic, D., Sher, A., Radtke, F., Souabni, A., Busslinger, M., McCright, B., Gridley, T., & Flavell, R. A.
Affiliations: Yale University (US)
National Institutes of Health (US)
ISREC Foundation (CH)
Research Institute of Molecular Pathology (AT)
Jackson Laboratory (US)
Howard Hughes Medical Institute (US)
Corresponding author: Amsen, Derk
ORCID: Amsen, Derk
Jankovic, Dragana
Sher, Alan
Radtke, Freddy
Busslinger, Meinrad
McCright, Brent
Flavell, Richard A.
Venue: Immunity
Publisher: Elsevier BV
Published: 2007-07
Volume: 27
Issue: 1
Pages: 89-99
ISSN: 1074-7613 (ISSN-L)
DOI: 10.1016/j.immuni.2007.05.021
PMC: PMC2062505
OpenAlex: W2042784167
Cited by: 396
References: 73
Citations by year: 2026: 5 · 2025: 4 · 2024: 5 · 2023: 7 · 2022: 17 · 2021: 11 · 2020: 11 · 2019: 13 · 2018: 13 · 2017: 19 · 2016: 25 · 2015: 22 · 2014: 21 · 2013: 37 · 2012: 33
FWCI: 15.36
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, 2208 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)
PubMed Central (acceptedVersion)
Data Archiving and Networked Services (DANS) (submittedVersion)
Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
IRIS (submittedVersion)
The Mouseion at the JAXlibrary (Jackson Laboratory) (submittedVersion)
Pure Amsterdam UMC (submittedVersion)
SERVAL (Université de Lausanne) (submittedVersion)
Funders: American Diabetes Association
National Institutes of Health (NS036437)
Topics: Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
Keywords: GATA3, Notch signaling, T helper cell differentiation, Th1 differentiation, Th2 differentiation, CD4+ T cells, RBPJ, Notch1, Notch2, parasite antigens, transcriptional regulation
MeSH terms: Animals, Base Sequence, Cell Differentiation, Cells, Cultured, T-Lymphocytes, Helper-Inducer, Humans, Mice, Inbred C57BL, Mice, Transgenic, Molecular Sequence Data, Signal Transduction, Mice, Knockout, Th1 Cells, Th2 Cells, GATA3 Transcription Factor, Mice, Immunoglobulin J Recombination Signal Sequence-Binding Protein, Receptors, Notch

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Direct Regulation of Gata3 Expression Determines the T Helper Differentiation Potential of Notch

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