ArticleThe Journal of biological chemistry2013
T cell receptor (TCR) and transforming growth factor β (TGF-β) signaling converge on DNA (cytosine-5)-methyltransferase to control forkhead box protein 3 (foxp3) locus methylation and inducible regulatory T cell differentiation.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
33 citing papers in PubMed, 49 citations in OpenAlex.
- miRNA/mRNA analysis of increased TGF-β pathways drive epithelial-mesenchymal transition and regulatory T cell differentiation.Frontiers in immunology · 2026Article
- miRNA/mRNA analysis of increased TGF-β pathways drive epithelial-mesenchymal transition and regulatory T cell differentiation.bioRxiv : the preprint server for biology · 2025Article
- Immune-related gene methylation prognostic instrument for stratification and targeted treatment of ovarian cancer patients toward advanced 3PM approach.The EPMA journal · 2024Article
- Massage on the prevention of breast cancer through stress reduction and enhancing immune system.Breast disease · 2024Review
- Protein phosphatase 6 (Pp6) is crucial for regulatory T cell function and stability in autoimmunity.Genes & diseases · 2022Article
- In Vitro Analysis of TGF-β Signaling Modulation of Porcine Alveolar Macrophages in Porcine Circovirus Type 2b Infection.Veterinary sciences · 2022Article
- Epigenetic regulation and T-cell responses in endometriosis - something other than autoimmunity.Frontiers in immunology · 2022Review
- Exosome-Derived MicroRNAs of Human Milk and Their Effects on Infant Health and Development.Biomolecules · 2021Review
- Highly Purified Alloantigen-Specific Tregs From Healthy and Chronic Kidney Disease Patients Can Be Long-Term Expanded, Maintaining a Suppressive Phenotype and Function in the Presence of Inflammatory Cytokines.Frontiers in immunology · 2021Article
- Epigenetic regulation of prostate cancer.Genes & diseases · 2020Review
- DNMT1 mutations leading to neurodegeneration paradoxically reflect on mitochondrial metabolism.Human molecular genetics · 2020Article
- Tolerogenic Effect Elicited by Protein Fraction Derived From Different Formulas for Dietary Treatment of Cow's Milk Allergy in Human Cells.Frontiers in immunology · 2020Article
- From stability to dynamics: understanding molecular mechanisms of regulatory T cells through Foxp3 transcriptional dynamics.Clinical and experimental immunology · 2019Review
- Redox, immune and genetic biomarker system for personalized treatments in colorectal cancer.World journal of gastrointestinal oncology · 2019Article
- DNA methylation in the central and efferent limbs of the chemoreflex requires carotid body neural activity.The Journal of physiology · 2018Article
- Suppression of IL-17F, but not of IL-17A, provides protection against colitis by inducing TNature immunology · 2018Article
- Reciprocal Regulation of Glycolysis-Driven Th17 Pathogenicity and Regulatory T Cell Stability by Cdc42.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- The -Frontiers in immunology · 2018Article
- Critical Role of TGF-β and IL-2 Receptor Signaling in Foxp3 Induction by an Inhibitor of DNA Methylation.Frontiers in immunology · 2018Article
- Zebularine Promotes Hepatic Differentiation of Rabbit Bone Marrow Mesenchymal Stem Cells by Interfering with p38 MAPK Signaling.Stem cells international · 2018Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Naïve T cells can be induced to differentiate into Foxp3(+) regulatory T cells (iTregs) upon suboptimal T cell receptor (TCR) stimulus or TCR stimulus in conjunction with TGF-β signaling; however, we do not fully understand how these signals coordinately control foxp3 expression. Here, we show that strong TCR activation, in terms of both duration and ligand affinity, causes the accumulation of DNA (cytosine-5)-methyltransferase 1 (DNMT1) and DNMT3b and their specific enrichment at the foxp3 locus, which leads to increased CpG methylation and inhibits foxp3 transcription. During this process the augmentation of DNMT1 is regulated through at least two post-transcriptional mechanisms; that is, strong TCR signal inactivates GSK3β to rescue DNMT1 protein from proteasomal degradation, and strong TCR signal suppresses miR-148a to derepress DNMT1 mRNA translation. Meanwhile, TGF-β signaling antagonizes DNMT1 accumulation via activation of p38 MAP kinase. Thus, independent of transcription factor activation, TCR and TGF-β signals converge on DNMT1 to modulate the expression of foxp3 epigenetically, which marks mother cell iTreg lineage choice within the genome of differentiating daughter cells.
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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.