ArticleProceedings of the National Academy of Sciences of the United States of America2024
DNA hypomethylation ameliorates erosive inflammatory arthritis by modulating interferon regulatory factor-8.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
5 citing papers in PubMed, 7 citations in OpenAlex.
- Immune-mediated rheumatoid arthritis: from single-cell genomics to new therapies.Nature immunology · 2026Review
- Epigenetic Alterations in Microbiome-Host Interactions in Inflammatory and Autoimmune Diseases.International journal of molecular sciences · 2026Review
- Propagation of monocyte exhaustion memory and underlying mechanisms.Cell communication and signaling : CCS · 2025Article
- Review
- 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
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Epigenetic regulation plays a crucial role in the pathogenesis of autoimmune diseases such as inflammatory arthritis. DNA hypomethylating agents, such as decitabine (DAC), have been shown to dampen inflammation and restore immune homeostasis. In the present study, we demonstrate that DAC elicits potent anti-inflammatory effects and attenuates disease symptoms in several animal models of arthritis. Transcriptomic and epigenomic profiling show that DAC-mediated hypomethylation regulates a wide range of cell types in arthritis, altering the differentiation trajectories of anti-inflammatory macrophage populations, regulatory T cells, and tissue-protective synovial fibroblasts (SFs). Mechanistically, DAC-mediated demethylation of intragenic 5'-Cytosine phosphate Guanine-3' (CpG) islands of the transcription factor Irf8 (interferon regulatory factor 8) induced its re-expression and promoted its repressor activity. As a result, DAC restored joint homeostasis by resetting the transcriptomic signature of negative regulators of inflammation in synovial macrophages (MerTK, Trem2, and Cx3cr1), T
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