{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T18:27:02Z","timestamp":1793125622262,"version":"4.5.0"},"reference-count":136,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>N6-methyladenosine (m6A) methylation is the most common intramolecular modification in eukaryotic mRNA; its dynamic regulation depends on \u201cwriters\u201d (methyltransferases: METTL3\/METTL14\/WTAP\/VIRMA), \u201cerasers\u201d (demethylases: FTO\/ALKBH5), and \u201creaders\u201d (binding proteins: YTHDF\/YTHDC\/IGF2BP families), thereby regulating RNA splicing, nuclear export, translation, and degradation. In rheumatoid arthritis (RA), this epigenetic network is severely disrupted: abnormal expression of writers leads to post-transcriptional activation of pro-inflammatory genes, while an imbalance in erasers compromises the stability of mRNAs encoding key signaling molecules. Together, these factors promote abnormal differentiation of immune cells, invasive proliferation of fibroblast-like synovial cells, and cartilage erosion. At the same time, hypoxia, inflammatory cytokines, and metabolic stress present in the joint microenvironment of RA induce cellular metabolic reprogramming, characterized by a shift toward aerobic glycolysis (Warburg effect), a reorganization of lipid synthesis and oxidation pathways, and an increase in glutamine uptake and catabolism; these changes all contribute to accelerating disease progression. Recent data have revealed a foundational integration between m6A modification and metabolic reprogramming: m6A regulators directly reshape the metabolic network by targeting transcripts encoding the glycolysis-limiting enzyme (HK2), key molecules in lipid metabolism (FASN\/CPT1), and amino acid transporters (SLC1A5), thereby coordinating immune inflammation and tissue destruction in RA. This review elucidates the regulatory role of m6A methylation in the metabolic reprogramming of RA and explains how writers, erasers, and readers influence disease progression by participating in glycolysis, lipid metabolism, and glutamine metabolism. By focusing on the central question of whether m6A modification is the root cause of metabolic reprogramming in the pathogenesis of RA, we have integrated existing data to define the \u201cm6A-metabolism-immunity\u201d regulatory axis and identified potential therapeutic strategies targeting this association.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1834919","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T05:56:47Z","timestamp":1778651807000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Immunometabolic reprogramming in rheumatoid arthritis: the epitranscriptomic role of N6-methyladenosine in innate and adaptive immunity"],"prefix":"10.3389","volume":"17","author":[{"given":"Jin","family":"Yang","sequence":"first","affiliation":[{"name":"The First Affiliated Hospital of Anhui University of Chinese Medicine","place":["Hefei, Anhui, China"]},{"name":"Anhui University of Chinese 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China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuwei","family":"Zhou","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Anhui University of Chinese Medicine","place":["Hefei, Anhui, China"]},{"name":"Anhui University of Chinese Medicine First Clinical Medical College","place":["Hefei, Anhui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"18001","DOI":"10.1038\/nrdp.2018.1","article-title":"Rheumatoid arthritis","volume":"4","author":"Smolen","year":"2018","journal-title":"Nat Rev Dis Primers"},{"key":"B2","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1038\/nri.2016.124","article-title":"The immunopathogenesis of seropositive rheumatoid arthritis: from triggering to targeting","volume":"17","author":"Malmstr\u00f6m","year":"2017","journal-title":"Nat Rev 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