ArticleThe EMBO journal1997
T-cell subset-specific expression of the IL-4 gene is regulated by a silencer element and STAT6.
Article in The EMBO journal, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 130 citations in OpenAlex.
- Potential Natural Biomolecules Targeting JAK/STAT/SOCS Signaling in the Management of Atopic Dermatitis.Molecules (Basel, Switzerland) · 2022Review
- Modeling TImmunological reviews · 2017Review
- T Helper Subsets, Peripheral Plasticity, and the Acute Phase Protein, α1-Antitrypsin.BioMed research international · 2015Review
- Mycoplasma pneumoniae modulates STAT3-STAT6/EGFR-FOXA2 signaling to induce overexpression of airway mucins.Infection and immunity · 2014Article
- STAT4 and T-bet are required for the plasticity of IFN-γ expression across Th2 ontogeny and influence changes in Ifng promoter DNA methylation.Journal of immunology (Baltimore, Md. : 1950) · 2013Article
- Requirement of interaction between mast cells and skin dendritic cells to establish contact hypersensitivity.PloS one · 2011Article
- DNA methylation and not allelic variation regulates STAT6 expression in human T cells.Clinical and experimental medicine · 2010Article
- Article
- Oncostatin M regulates secretoglobin 3A1 and 3A2 expression in a bidirectional manner.American journal of respiratory cell and molecular biology · 2009Article
- Interferon regulatory factor 4 differentially regulates the production of Th2 cytokines in naive vs. effector/memory CD4+ T cells.Proceedings of the National Academy of Sciences of the United States of America · 2008Article
- Regulation of the Il4 gene is independently controlled by proximal and distal 3' enhancers in mast cells and basophils.Molecular and cellular biology · 2007Article
- Repression of interleukin-4 in T helper type 1 cells by Runx/Cbf beta binding to the Il4 silencer.The Journal of experimental medicine · 2007Article
- Suppressor of cytokine signaling 3 (SOCS3) in Th2 cells evokes Th2 cytokines, IgE, and eosinophilia.Current allergy and asthma reports · 2006Review
- A role of suppressor of cytokine signaling 3 (SOCS3/CIS3/SSI3) in CD28-mediated interleukin 2 production.The Journal of experimental medicine · 2003Article
- Expression of the suppressor of cytokine signaling-5 (SOCS5) negatively regulates IL-4-dependent STAT6 activation and Th2 differentiation.Proceedings of the National Academy of Sciences of the United States of America · 2002Article
- JAK-STAT signaling in asthma.The Journal of clinical investigation · 2002Review
- GATA-3 induces T helper cell type 2 (Th2) cytokine expression and chromatin remodeling in committed Th1 cells.The Journal of experimental medicine · 2000Article
- T cell receptor-induced calcineurin activation regulates T helper type 2 cell development by modifying the interleukin 4 receptor signaling complex.The Journal of experimental medicine · 2000Article
- A stimulus-specific role for CREB-binding protein (CBP) in T cell receptor-activated tumor necrosis factor alpha gene expression.Proceedings of the National Academy of Sciences of the United States of America · 2000Article
- Characterization of a novel negative regulatory element in the human interleukin 4 promoter.Leukemia · 2000Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
During development of CD4+ T lymphocytes in the periphery, differential expression of cytokine genes, such as those of interleukin (IL)-2 and IL-4, occurs in distinct T-cell subsets. IL-4 is a cytokine produced by T-helper 2 (Th2) cells, and the IL-4 receptor (IL-4R)-mediated signaling pathway is thought to be required for commitment to the Th2 phenotype. However, the molecular basis for development of the Th subset-specific production of IL-4 remains unclear. We demonstrate here that the IL-4 promoter is functional in Th1 and B cells which do not normally form IL-4 transcripts as well as in IL-4-producing T cells. Based on studies of the effect of several different upstream and downstream regions of the IL-4 gene on IL-4 promoter activity, a Th1-specific IL-4 silencer element was identified in the 3'-untranslated region. The silencer region contained a consensus sequence for a transcriptional factor that is normally regulated by the IL-4 R signaling pathway, STAT6. Nuclear expression of STAT6 protein, which was shown to bind to the silencer region, was observed in Th2 cells but not in Th1 cells. Deletion of the STAT6-binding site from the silencer region and inhibition of STAT6 function resulted in the appearance of silencing function even in Th2 cells. These results provide evidence that the silencer element, and the binding of STAT6 to this element, play a permissive role in determining the commitment into Th2 phenotype.
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