ArticleFrontiers in immunology2020
Targeted De-Methylation of the FOXP3-TSDR Is Sufficient to Induce Physiological FOXP3 Expression but Not a Functional Treg Phenotype.
Article in Frontiers in immunology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 65 citations in OpenAlex.
- Trial
- Cytokine-independent activation of STAT5 promotes the persistence and function of CD4Molecular therapy. Advances · 2026Article
- The Role of Chimeric Antigen Receptor Regulatory T Cells in Promoting Immune Tolerance in Solid Organ Transplantation:Saudi medical journal · 2026Review
- Dysregulated IL-2 signaling and T-cell subset shifts are associated with eosinophilic esophagitis activity.Biochemistry and biophysics reports · 2026Article
- Integrated epigenetic and genetic programming of primary human T cells.Nature biotechnology · 2026Article
- DNA Methylation as a Programmable Information Layer: From Molecular Marks to Disease State Engineering.International journal of molecular sciences · 2026Review
- Precision Immunoregulation in transplantation: The rise of engineered Treg therapies.Molecular biology reports · 2026Review
- Engineering CAR-Tregs with Phage-Selected scFv Enables a New Paradigm for Immune Regulation.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026Review
- Next-Generation regulatory T cell therapies: Translational considerations for inflammatory bowel disease.Human immunology · 2026Review
- CD38 expression by neonatal human naive CD4+ T cells shapes their distinct metabolic and tolerogenic properties.The Journal of clinical investigation · 2026Article
- Epigenetic editing: from concept to clinic.Nature reviews. Drug discovery · 2026Review
- Epigenetic editing to advance CAR T cell therapy.Clinical epigenetics · 2026Review
- Tissue repair in the central nervous system: the epigenetic programming of regulatory T cells.Frontiers in immunology · 2026Review
- Regulatory T cell therapy in solid organ transplantation: mechanisms, translational progress, and remaining barriers.Frontiers in immunology · 2026Review
- Regulatory T cell therapy in autoimmune and immune-mediated diseases: from basic research to clinical practice and future perspectives.Frontiers in immunology · 2026Review
- Increased phenotypic and functional stability of human allospecific induced Tregs is associated with Vitamin C-mediatedFrontiers in immunology · 2026Article
- Regulatory T cell dysfunction and exhaustion in uveitis: immunometabolic mechanisms, microenvironmental drivers, and emerging therapeutic strategies.Frontiers in immunology · 2026Review
- Review
- Targeting the Th17/Treg axis: from immunological insights to therapeutic avenues in atherosclerosis.Frontiers in immunology · 2026Review
- Regulatory T cells in breast cancer drivers of immune suppression and targets for immunotherapy.Frontiers in immunology · 2026Review
2 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CD4+ regulatory T cells (Tregs) are key mediators of immunological tolerance and promising effector cells for immuno-suppressive adoptive cellular therapy to fight autoimmunity and chronic inflammation. Their functional stability is critical for their clinical utility and has been correlated to the demethylated state of the TSDR/CNS2 enhancer element in the Treg lineage transcription factor FOXP3. However, proof for a causal contribution of the TSDR de-methylation to FOXP3 stability and Treg induction is so far lacking. We here established a powerful transient-transfection CRISPR-Cas9-based epigenetic editing method for the selective de-methylation of the TSDR within the endogenous chromatin environment of a living cell. The induced de-methylated state was stable over weeks in clonal T cell proliferation cultures even after expression of the editing complex had ceased. Epigenetic editing of the TSDR resulted in FOXP3 expression, even in its physiological isoform distribution, proving a causal role for the de-methylated TSDR in FOXP3 regulation. However, successful FOXP3 induction was not associated with a switch towards a functional Treg phenotype, in contrast to what has been reported from FOXP3 overexpression approaches. Thus, TSDR de-methylation is required, but not sufficient for a stable Treg phenotype induction. Therefore, targeted demethylation of the TSDR may be a critical addition to published
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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.