ArticleThe Journal of clinical investigation2020
Maintenance DNA methylation is essential for regulatory T cell development and stability of suppressive function.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
What it found
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Who cites it
62 citing papers in PubMed.
- Targeting FOXP3 and Regulatory T Cells in Systemic Lupus Erythematosus: Emerging Therapeutic Strategies and Clinical Prospects.Journal of cellular biochemistry · 2026Review
- Maintenance DNA methylation is necessary for age-related alterations in regulatory T cell transcriptional and DNA methylation signatures.bioRxiv : the preprint server for biology · 2026Article
- Clinical development of tacrolimus-resistant regulatory T cells to enable simultaneous immunosuppression and immune regulation.Molecular therapy. Advances · 2026Article
- Umbilical cord blood cell transcriptional and methylation signatures at birth are associated with BPD development and chorioamnionitis: a pilot study.Scientific reports · 2026Article
- Hypoxia regulates Th17/Treg balance by altering chromatin accessibility and gene expression.The FEBS journal · 2026Article
- Review
- Targeting regulatory T cells in glioblastoma: from mechanistic insights to novel immunotherapeutic strategies.Frontiers in immunology · 2026Review
- Long-term DNA methylation changes induced by age and elevated COSkeletal muscle · 2025Article
- STAT6 inhibition stabilizes induced regulatory T cells and enhances their therapeutic potential in inflammatory bowel disease.Immunologic research · 2025Article
- Umbilical Cord Blood Cell Transcriptional and Methylation Signatures at Birth Are Associated with BPD Development.bioRxiv : the preprint server for biology · 2025Article
- Tregs epigenetically reprogrammed from autoreactive effector T cells mitigate established autoimmunity.JCI insight · 2025Article
- UHRF1 in Immune Regulation and Diseases: Mechanisms and Therapeutic Implications.Clinical reviews in allergy & immunology · 2025Review
- T-cell differentiation stage block bias confers hypermethylation and mediastinal preference in T-cell lymphoblastic lymphoma.Clinical and translational medicine · 2025Article
- The flux of energy in critical illness and the obesity paradox.Physiological reviews · 2025Review
- Novel enzyme-based reduced representation method for DNA methylation profiling with low inputs.Nucleic acids research · 2025Article
- AMPK is necessary for Treg functional adaptation to microenvironmental stress during malignancy and viral pneumonia.The Journal of clinical investigation · 2025Article
- Hyperactivating EZH2 to augment H3K27me3 levels in regulatory T cells enhances immune suppression by driving early effector differentiation.Cell reports · 2024Article
- Review
- The E3 ubiquitin-protein ligase UHRF1 promotes adipogenesis and limits fibrosis by suppressing GPNMB-mediated TGF-β signaling.Scientific reports · 2024Article
- Single cell characterization of blood and expanded regulatory T cells in autoimmune polyendocrine syndrome type 1.iScience · 2024Article
2 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
Tregs require Foxp3 expression and induction of a specific DNA hypomethylation signature during development, after which Tregs persist as a self-renewing population that regulates immune system activation. Whether maintenance DNA methylation is required for Treg lineage development and stability and how methylation patterns are maintained during lineage self-renewal remain unclear. Here, we demonstrate that the epigenetic regulator ubiquitin-like with plant homeodomain and RING finger domains 1 (Uhrf1) is essential for maintenance of methyl-DNA marks that stabilize Treg cellular identity by repressing effector T cell transcriptional programs. Constitutive and induced deficiency of Uhrf1 within Foxp3+ cells resulted in global yet nonuniform loss of DNA methylation, derepression of inflammatory transcriptional programs, destabilization of the Treg lineage, and spontaneous inflammation. These findings support a paradigm in which maintenance DNA methylation is required in distinct regions of the Treg genome for both lineage establishment and stability of identity and suppressive function.
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Registered trials
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