ArticleInflammation2024
Targeted Demethylation of FOXP3-TSDR Enhances the Suppressive Capacity of STAT6-deficient Inducible T Regulatory Cells.
Article in Inflammation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- Regulatory T Cells in Peri-implant Diseases: Current Osteoimmunologic Perspectives and Translational Challenges.Tissue engineering and regenerative medicine · 2026Review
- Regulatory T cell induction strategies and applications in the treatment of immune and non-immune diseases.Signal transduction and targeted therapy · 2026Review
- Review
- TET Enzymes as Epigenetic Integrators in Intestinal Immunity, Inflammation, and Disease.Journal of personalized medicine · 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
- Regulatory T Cell Heterogeneity in the Steady State and Tumor.Immune network · 2026Review
- Beyond Foxp3 and TSDR: a dual epigenetic lock framework for treg stability and plasticity.Frontiers in immunology · 2026Review
- Microbiota-directed therapies for atopic dermatitis: a three-tier framework for inflammation control, immune modulation, and microbiome restoration.Frontiers in immunology · 2026Review
- Regulatory T cells in autoimmune diseases: biological mechanisms, clinical translation, and translational challenges.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
- STAT6 inhibition stabilizes induced regulatory T cells and enhances their therapeutic potential in inflammatory bowel disease.Immunologic research · 2025Article
- Rewiring immune suppression in NSCLC: Roles and plasticity of Tregs and Th17 cells.Frontiers in immunology · 2025Review
- CAR-based cell therapy for autoimmune diseases.Frontiers in immunology · 2025Review
- Promotion of Treg/Th17 balance in MRL/lpr mice by Jianpi-Zishen Formula via modulation of DNMT1-mediated Foxp3 methylation.Frontiers in immunology · 2025Article
- CRISPR/Cas9 technology in tumor research and drug development application progress and future prospects.Frontiers in pharmacology · 2025Review
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
In vitro induced T regulatory cells (iTregs) are promising for addressing inflammation-driven diseases. However, current protocols for the generation and expansion of iTregs fail to induce extensive demethylation of the Treg-specific demethylated region (TSDR) within the FOXP3 gene, recognized as the master regulator for regulatory T cells (Tregs). This deficiency results in the rapid loss of Foxp3 expression and an unstable regulatory phenotype. Nevertheless, inhibition of STAT6 signaling effectively stabilizes Foxp3 expression in iTregs. Thus, this study aimed to develop a protocol combining epigenetic editing with STAT6 deficiency to improve iTregs' ability to maintain stable suppressive function and a functional phenotype. Our findings demonstrate that the combination of STAT6 deficiency (STAT6-/-) with targeted demethylation of the TSDR using a CRISPR-TET1 tool leads to extensive demethylation of FOXP3-TSDR. Demethylation in STAT6-/- iTregs was associated with enhanced expression of Foxp3 and suppressive markers such as CTLA-4, PD-1, IL-10, and TGF-β. Furthermore, the edited STAT6-/- iTregs exhibited an increased capacity to suppress CD8+ and CD4+ lymphocytes and could more efficiently impair Th1-signature gene expression compared to conventional iTregs. In conclusion, the deactivation of STAT6 and TSDR-targeted demethylation via CRISPR-TET1 is sufficient to induce iTregs with heightened stability and increased suppressive capacity, offering potential applications against inflammatory and autoimmune diseases.
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