ArticleInternational immunology2017
Improvement of Foxp3 stability through CNS2 demethylation by TET enzyme induction and activation.
Article in International immunology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 74 citations in OpenAlex.
- Tet2 deficiency drives age-related heterogeneous progression of myeloid neoplasms through epigenetic-immune microenvironment imbalance.Journal of translational medicine · 2026Article
- Ogonto, a traditional Japanese herbal medicine, attenuates food allergy symptoms in mice through the induction of regulatory T cells.Journal of natural medicines · 2026Article
- Review
- Roles of the Altitude-Adapted Immune Microenvironment in Pulmonary Vascular Remodeling in High-Altitude Pulmonary Hypertension: A Review.Medical science monitor : international medical journal of experimental and clinical research · 2026Review
- Beyond Foxp3 and TSDR: a dual epigenetic lock framework for treg stability and plasticity.Frontiers in immunology · 2026Review
- Regulatory T cell therapy in solid organ transplantation: mechanisms, translational progress, and remaining barriers.Frontiers in immunology · 2026Review
- Increased phenotypic and functional stability of human allospecific induced Tregs is associated with Vitamin C-mediatedFrontiers in immunology · 2026Article
- CRISPR tools for T cells: targeting the genome, epigenome, and transcriptome.Trends in cancer · 2025Review
- Fine tuning towards the next generation of engineered T cells.Nature biomedical engineering · 2025Review
- T Cell Resistance: On the Mechanisms of T Cell Non-activation.Immune network · 2024Review
- Regulatory T lymphocytes as a treatment method for rheumatoid arthritis - Superiority of allogeneic to autologous cells.Heliyon · 2024Review
- Epigenetics and immunotherapy in colorectal cancer: progress and promise.Clinical epigenetics · 2024Review
- Improving regulatory T cell production through mechanosensing.Journal of biomedical materials research. Part A · 2024Article
- CRIF1 deficiency induces FOXP3Science advances · 2024Article
- Epigenetic Approaches to Identifying Asthma Endotypes.Allergy, asthma & immunology research · 2024Review
- T-regulatory cells require Sin3a for stable expression of Foxp3.Frontiers in immunology · 2024Article
- Deciphering the developmental trajectory of tissue-resident Foxp3Frontiers in immunology · 2024Review
- Modulating Treg stability to improve cancer immunotherapy.Trends in cancer · 2023Review
- Transcriptional and Epigenetic Regulation of Context-Dependent Plasticity in T-Helper Lineages.Immune network · 2023Review
- Regulatory T cells as a therapeutic approach for inflammatory bowel disease.European journal of immunology · 2023Review
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
Since induced regulatory T cells (iTregs) can be produced in a large quantity in vitro, these cells are expected to be clinically useful to induce immunological tolerance in various immunological diseases. Foxp3 (Forkhead box P3) expression in iTregs is, however, unstable due to the lack of demethylation of the CpG island in the conserved non-coding sequence 2 (CNS2) of the Foxp3 locus. To facilitate the demethylation of CNS2, we over-expressed the catalytic domain (CD) of the ten-eleven translocation (TET) protein, which catalyzes the steps of the iterative demethylation of 5-methylcytosine. TET-CD over-expression in iTregs resulted in partial demethylation of CNS2 and stable Foxp3 expression. We also discovered that TET expression was enhanced under low oxygen (5%) culture conditions, which facilitated CNS2 DNA demethylation and stabilization of Foxp3 expression in a TET2- and TET3-dependent manner. In combination with vitamin C treatment, which has been reported to enhance TET catalytic activity, iTregs generated under low oxygen conditions retained more stable Foxp3 expression in vitro and in vivo and exhibited stronger suppression activity in a colitis model compared with untreated iTregs. Our data indicate that the induction and activation of TET enzymes in iTregs would be an effective method for Treg-mediated adoptive immunotherapy.
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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.