Direct regulation of Gata3 expression determines the T helper differentiation potential of Notch
Open accessAbstract
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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GATA3 expression can also be induced by T cell receptor (TCR) signaling and other pathways, such as Notch and WNT signaling.
“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].”
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Notch Targets and Their Regulation
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Notch Signaling Regulates Mouse and Human Th17 Differentiation
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Notch Signaling Specifies Megakaryocyte Development from Hematopoietic Stem Cells
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In vivo studies fail to reveal a role for IL-4 or STAT6 signaling in Th2 lymphocyte differentiation
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Notch Simultaneously Orchestrates Multiple Helper T Cell Programs Independently of Cytokine Signals
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Control of peripheral tolerance by regulatory T cell–intrinsic Notch signaling
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Notch1 Signaling in FIZZ1 Induction of Myofibroblast Differentiation
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Engineering the IL ‐4/ IL ‐13 axis for targeted immune modulation
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A central role for Notch in effector CD8+ T cell differentiation
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Self-citationNotch Signalling in Breast Development and Cancer
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Notch signaling distinguishes 2 waves of definitive hematopoiesis in the zebrafish embryo
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Protein kinase CK2 enables regulatory T cells to suppress excessive TH2 responses in vivo
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On the hunt for helminths: innate immune cells in the recognition and response to helminth parasites
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Notch Signaling as a Regulator of the Tumor Immune Response: To Target or Not To Target?
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Notch Signaling Regulates Immune Responses in Atherosclerosis
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Self-citationγ-Secretase Inhibitor Reduces Allergic Pulmonary Inflammation by Modulating Th1 and Th2 Responses
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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
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2007-07
- Volume
- 27
- Issue
- 1
- Pages
- 89-99
- ISSN
- 1074-7613 (ISSN-L)
- 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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