ArticleNature medicine2013
Phosphorylation of FOXP3 controls regulatory T cell function and is inhibited by TNF-α in rheumatoid arthritis.
Article in Nature medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 296 papers, 1 of them a synthesis that pooled it.
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Who cites it
296 citing papers in PubMed, 1 synthesis or guideline pooled it, 506 citations in OpenAlex.
- Genetic Risk Factors for Nontuberculous Mycobacterial Pulmonary Disease (Systematic Review).Sovremennye tekhnologii v meditsine · 2024Pooled it
- Changes in lung immune cells related to clinical outcome during treatment with infliximab for sarcoidosis.Clinical and experimental immunology · 2020Trial
- Risk variants disrupting enhancers of TProceedings of the National Academy of Sciences of the United States of America · 2019Trial
- Protein Posttranslational Modifications in Immunity: Molecular Mechanisms and Therapeutic Targets.MedComm · 2026Review
- Why regulatory T cells fail to control inflammation in rheumatoid arthritis.Nature immunology · 2026Article
- Regulatory T cells as a potential treatment for autoimmune inflammatory rheumatic and musculoskeletal diseases.Clinical rheumatology · 2026Review
- Elucidation of the Effects of Heat Treatment on Polyphenolic Compounds in Highland Barley and Their Potential Mechanisms of Action in Improving Hypertension Using Targeted Metabolomics, Network Pharmacology, and Molecular Docking.Foods (Basel, Switzerland) · 2026Article
- Article
- Association ofInternational journal of molecular sciences · 2026Article
- Promising TNF-α inhibitors: Targeting pathogenic TNF-α/TNFR signaling to restore Th17/Treg balance in rheumatoid arthritis.Journal of pharmaceutical analysis · 2026Review
- Sulfated polysaccharide facilitates macrophage-Treg crosstalk to mitigate chronic inflammation in diabetic wound healing.Bioactive materials · 2026Article
- Proanthocyanidins in immune-mediated inflammatory diseases: molecular mechanisms and therapeutic potential.Frontiers in pharmacology · 2026Review
- Effects of TNF-α, IL-1β and IL-2 on regulatory T cells in children with idiopathic nephrotic syndrome.Frontiers in pediatrics · 2026Article
- Historical evaluation of clinical outcomes and safety following isolated limb perfusion for unresectable melanoma: Real-world data from the Mannheim Cancer Center.Therapeutic advances in medical oncology · 2026Article
- Macrophage-centred crosstalk with infiltrating immune cells in rheumatoid arthritis and its regulation by mesenchymal stem cells.Journal of translational medicine · 2025Review
- Review
- Functional and dysfunctional T regulatory cell states in human tissues in RA and other autoimmune arthritic diseases.bioRxiv : the preprint server for biology · 2025Article
- Evaluating the predictive potential of Th1 (IFN-γJournal of neurology · 2025Article
- Integrating network pharmacology and experimental validation to explore the mechanism of Yiqi Ziyin in treating immune thrombocytopenia.Scientific reports · 2025Article
- A Proteomics Outlook on the Molecular Effectors of CAR-T Cell Therapy in Cancer Management.Journal of proteome research · 2025Review
236 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Regulatory T (Treg) cells suppress autoimmune disease, and impaired Treg cell function is associated with rheumatoid arthritis. Here we demonstrate that forkhead box P3 (FOXP3) transcriptional activity and, consequently, Treg cell suppressive function are regulated by phosphorylation at Ser418 in the C-terminal DNA-binding domain. In rheumatoid arthritis-derived Treg cells, the Ser418 site was specifically dephosphorylated by protein phosphatase 1 (PP1), whose expression and enzymatic activity were induced in the inflamed synovium by tumor necrosis factor α (TNF-α), leading to impaired Treg cell function. Moreover, TNF-α-induced Treg cell dysfunction correlated with increased numbers of interleukin-17 (IL-17)(+) and interferon-γ (IFN-γ)(+)CD4(+) T cells within the inflamed synovium in rheumatoid arthritis. Treatment with a TNF-α-specific antibody restored Treg cell function in subjects with rheumatoid arthritis, which was associated with decreased PP1 expression and increased FOXP3 phosphorylation in Treg cells. Thus, TNF-α controls the balance between Treg cells and pathogenic TH17 and TH1 cells in the synovium of individuals with rheumatoid arthritis through FOXP3 dephosphorylation.
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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.