ArticleProceedings of the National Academy of Sciences of the United States of America2014
MeCP2 enforces Foxp3 expression to promote regulatory T cells' resilience to inflammation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 63 citations in OpenAlex.
- Mechanisms of Inflammation Chronification: Gene and Epigenetic Regulation of Intolerant Response (Trained Immunity).Current medicinal chemistry · 2026Article
- Identification of Regulators for Antigen-Specific CD8Veterinary sciences · 2025Article
- Rett syndrome: advances in Understanding MeCP2 function, potential gene therapies, and public health implications.Molecular biology reports · 2025Review
- Versatile functions of methyl-CpG-binding domain 2 (MBD2) in cellular characteristics and differentiation.Molecular biology reports · 2025Review
- Rett Syndrome: Thinking Beyond Brain Borders.Advances in experimental medicine and biology · 2025Review
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- Comprehensive analysis reveals the prognostic and immunogenic characteristics of DNA methylation regulators in lung adenocarcinoma.Respiratory research · 2024Article
- DNA demethylation in the hypothalamus promotes transcription of Agtr1a and Slc12a2 and hypertension development.The Journal of biological chemistry · 2024Article
- Methyl-CpG-Binding Protein 2 Emerges as a Central Player in Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorders.Cellular and molecular neurobiology · 2023Review
- Methyl-CpG binding domain 2 (Mbd2) is an epigenetic regulator of autism-risk genes and cognition.Translational psychiatry · 2023Article
- Multi-omic Profiling Reveals Early Immunological Indicators for Identifying COVID-19 Progressors.bioRxiv : the preprint server for biology · 2023Article
- Dawn-to-dusk dry fasting induces anti-atherosclerotic, anti-inflammatory, and anti-tumorigenic proteome in peripheral blood mononuclear cells in subjects with metabolic syndrome.Metabolism open · 2022Article
- DNA Methylation in Regulatory T Cell Differentiation and Function: Challenges and Opportunities.Biomolecules · 2022Review
- Methyl-CpG binding protein 2 is associated with the prognosis and mortality of elderly patients with hip fractures.Clinics (Sao Paulo, Brazil) · 2022Observational
- A single-cell atlas reveals the heterogeneity of meningeal immunity in a mouse model of Methyl CpG binding protein 2 deficiency.Frontiers in immunology · 2022Article
- Association between forkhead box P3 expression level and gender of Iranian juvenile idiopathic arthritis patients.Reumatologia · 2022Article
- CD98-induced CD147 signaling stabilizes the Foxp3 protein to maintain tissue homeostasis.Cellular & molecular immunology · 2021Article
- MeCP2 drives hepatocellular carcinoma progression via enforcing HOXD3 promoter methylation and expression through the HB-EGF/EGFR pathway.Molecular oncology · 2021Article
- MeCP2 deficiency exacerbates the neuroinflammatory setting and autoreactive response during an autoimmune challenge.Scientific reports · 2021Article
- MicroRNAs overexpressed in Crohn's disease and their interactions with mechanisms of epigenetic regulation explain novel aspects of Crohn's disease pathogenesis.Clinical epigenetics · 2021Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Forkhead box P3(+) (Foxp3(+)) regulatory T cells (Tregs) are crucial for peripheral tolerance. During inflammation, steady Foxp3 expression in Tregs is essential for maintaining their lineage identity and suppressive function. However, the molecular machinery governing Tregs' resilience to inflammation-induced Foxp3 destabilization remains elusive. Here, we demonstrate that methyl-CpG binding protein 2 (MeCP2), an eminent epigenetic regulator known primarily as the etiological factor of Rett syndrome, is critical to sustain Foxp3 expression in Tregs during inflammation. In response to inflammatory stimuli, MeCP2 is specifically recruited to the Conserved Non-Coding sequence 2 region of the foxp3 locus, where it collaborates with cAMP responsive element binding protein 1 to promote local histone H3 acetylation, thereby counteracting inflammation-induced epigenetic silencing of foxp3. Consequently, Treg-specific deletion of MeCP2 causes spontaneous immune activation in mice and failure in protection against autoimmunity. Furthermore, we demonstrate that Foxp3 expression in MeCP2-deficient Tregs diminishes with time, resulting in their failure to suppress effector T-cell-mediated colitis. Thus, MeCP2 serves as a critical safeguard that confers Tregs with resilience against inflammation.
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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.