ArticleProceedings of the National Academy of Sciences of the United States of America2021
Pharmacological modulation of T cell immunity results in long-term remission of autoimmune arthritis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 31 citations in OpenAlex.
- DNA methylation inhibitor decitabine ameliorates spondyloarthritis by suppressing Th17 responses and epigenetically upregulating VIPR1 in SKG mice.Arthritis research & therapy · 2026Article
- Integrating multi-omics, machine learning, and molecular dynamics simulations to identify glutamate metabolism-related biomarkers and drug candidates in rheumatoid arthritis.Frontiers in molecular biosciences · 2026Article
- The epigenetic landscape of rheumatoid arthritis: Pathogenesis and drug therapeutic potentials.Acta pharmaceutica Sinica. B · 2025Review
- Flavonoids as Immunoregulators: Molecular Mechanisms in Regulating Immune Cells and Their Therapeutic Applications in Inflammatory Diseases.Frontiers in immunology · 2025Review
- The dual role of tissue regulatory T cells in tissue repair: return to homeostasis or fibrosis.Frontiers in immunology · 2025Review
- Resolution of inflammation during rheumatoid arthritis.Frontiers in cell and developmental biology · 2025Review
- IRAK3 is upregulated in rheumatoid arthritis synovium and delays the onset of experimental arthritis.Frontiers in immunology · 2025Article
- Inflammatory disease status and response to TNF blockade are associated with mechanisms of endotoxin tolerance.Journal of autoimmunity · 2024Article
- Trichloroethylene metabolite modulates DNA methylation-dependent gene expression in Th1-polarized CD4+ T cells from autoimmune-prone mice.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
- DNA hypomethylation ameliorates erosive inflammatory arthritis by modulating interferon regulatory factor-8.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Single-cell RNA sequencing of mid-to-late stage spider embryos: new insights into spider development.BMC genomics · 2024Article
- Editorial: Exploring the role of T helper cells in autoimmune disease.Frontiers in immunology · 2024Article
- Review
- Signaling pathways in rheumatoid arthritis: implications for targeted therapy.Signal transduction and targeted therapy · 2023Review
- Unveiling tumor immune evasion mechanisms: abnormal expression of transporters on immune cells in the tumor microenvironment.Frontiers in immunology · 2023Review
- Topical drug delivery strategies for enhancing drug effectiveness by skin barriers, drug delivery systems and individualized dosing.Frontiers in pharmacology · 2023Review
- DNA Methylation of T Lymphocytes as a Therapeutic Target: Implications for Rheumatoid Arthritis Etiology.Frontiers in immunology · 2022Review
- Induction of IDO1 and Kynurenine by Serine Proteases Subtilisin, Prostate Specific Antigen, CD26 and HtrA: A New Form of Immunosuppression?Frontiers in immunology · 2022Article
- An integrated cytokine and kynurenine network as the basis of neuroimmune communication.Frontiers in neuroscience · 2022Review
- DNA methylation inhibitor resets tolerance in autoimmune arthritis.Nature reviews. Rheumatology · 2021Article
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Authors and funding
17 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chronic inflammatory diseases like rheumatoid arthritis are characterized by a deficit in fully functional regulatory T cells. DNA-methylation inhibitors have previously been shown to promote regulatory T cell responses and, in the present study, we evaluated their potential to ameliorate chronic and acute animal models of rheumatoid arthritis. Of the drugs tested, decitabine was the most effective, producing a sustained therapeutic effect that was dependent on indoleamine 2,3-dioxygenase (IDO) and was associated with expansion of induced regulatory T cells, particularly at the site of disease activity. Treatment with decitabine also caused apoptosis of Th1 and Th17 cells in active arthritis in a highly selective manner. The molecular basis for this selectivity was shown to be ENT1, a nucleoside transporter, which facilitates intracellular entry of the drug and is up-regulated on effector T cells during active arthritis. It was further shown that short-term treatment with decitabine resulted in the generation of a population of regulatory T cells that were able to suppress arthritis upon adoptive transfer. In summary, a therapeutic approach using an approved drug is described that treats active inflammatory disease effectively and generates robust regulatory T cells with the IDO-dependent capacity to maintain remission.
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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.