ArticleThe Journal of biological chemistry2008
STAT6 Inhibits TGF-beta1-mediated Foxp3 induction through direct binding to the Foxp3 promoter, which is reverted by retinoic acid receptor.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.
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Who cites it
85 citing papers in PubMed, 149 citations in OpenAlex.
- Regulatory T cell induction strategies and applications in the treatment of immune and non-immune diseases.Signal transduction and targeted therapy · 2026Review
- Targeting autocrine retinoic acid signaling by ALDH1A2 inhibition enhances antitumor dendritic cell vaccine efficacy.Nature immunology · 2026Article
- STAT6 inhibition stabilizes induced regulatory T cells and enhances their therapeutic potential in inflammatory bowel disease.Immunologic research · 2025Article
- Tregs epigenetically reprogrammed from autoreactive effector T cells mitigate established autoimmunity.JCI insight · 2025Article
- Targeted Demethylation of FOXP3-TSDR Enhances the Suppressive Capacity of STAT6-deficient Inducible T Regulatory Cells.Inflammation · 2024Article
- Lack of canonical thyroid hormone receptor α signaling changes regulatory T cell phenotype in female mice.iScience · 2024Article
- CD4+ T-cell subsets in autoimmune hepatitis: A review.Hepatology communications · 2023Review
- Regulatory T cells in peripheral tissue tolerance and diseases.Frontiers in immunology · 2023Review
- Intestinal factors promoting the development of RORγtFrontiers in immunology · 2023Review
- IL-4/IL-13 Axis in Allergic Rhinitis: Elevated Serum Cytokines Levels and Inverse Association With Tight Junction Molecules Expression.Frontiers in molecular biosciences · 2022Article
- IL-4 inhibits regulatory T cells differentiation by HDAC9-mediated epigenetic regulation.Cell death & disease · 2021Article
- STAT6 Is Critical for the Induction of Regulatory T Cells In Vivo Controlling the Initial Steps of Colitis-Associated Cancer.International journal of molecular sciences · 2021Article
- Ovalbumin-Derived Peptides Activate Retinoic Acid Signalling Pathways and Induce Regulatory Responses Through Toll-Like Receptor Interactions.Nutrients · 2020Article
- Treg expression of CIS suppresses allergic airway inflammation through antagonizing an autonomous TH2 program.Mucosal immunology · 2020Article
- BTLA-Expressing Dendritic Cells in Patients With Tuberculosis Exhibit Reduced Production of IL-12/IFN-α and Increased Production of IL-4 and TGF-β, Favoring Th2 and Foxp3Frontiers in immunology · 2020Article
- Foxp3 expression in induced regulatory T cells is stabilized by C/EBP in inflammatory environments.EMBO reports · 2018Article
- Helminth-Induced Production of TGF-β and Suppression of Graft-versus-Host Disease Is Dependent on IL-4 Production by Host Cells.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- STAT6 and Furin Are Successive Triggers for the Production of TGF-β by T Cells.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- TIM‑4 blockade of KCs combined with exogenous TGF‑β injection helps to reverse acute rejection and prolong the survival rate of mice receiving liver allografts.International journal of molecular medicine · 2018Article
- Aluminum Adjuvant-Containing Vaccines in the Context of the Hygiene Hypothesis: A Risk Factor for Eosinophilia and Allergy in a Genetically Susceptible Subpopulation?International journal of environmental research and public health · 2018Review
25 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
It has been shown that transforming growth factor beta1 (TGF-beta1) is critical in the generation of CD4(+)CD25(+)Foxp3(+)-inducible regulatory T cells (iTregs) from naïve CD4(+)T cells. However, in contrast to natural Tregs, TGF-beta1-induced iTregs rapidly lose both Foxp3 expression and suppression activity. We found that TGF-beta1-induced Foxp3 levels were maintained by the addition of the anti-interleukin 4 (IL-4) antibody or by STAT6 gene deletion. Thus, IL-4 is an important suppressor of Foxp3 induction, and T helper 2 development is a major cause for the disappearance of iTreg during long culture. Using promoter analysis in EL4 cells and primary T cells, we identified a silencer region containing a STAT6 binding site. STAT6 binding to this site reduced TGF-beta1-mediated Foxp3 promoter activation and chromatin modification. Retinoic acid has also been shown to suppress loss of Foxp3 induced by TGF-beta1. Retinoic acid in the presence of TGF-beta1 reduced STAT6 binding to the Foxp3 promoter and enhanced histone acetylation, thereby reverting the effect of IL-4. We propose that antagonistic agents for neutralizing IL-4 could be a novel strategy to facilitate inducible Treg cell generation and the promotion of tolerance in Th2-dominated diseases such as allergy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.