{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T17:00:17Z","timestamp":1788454817390,"version":"build-2803163510"},"reference-count":260,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T00:00:00Z","timestamp":1783036800000},"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>Immune-mediated diseases arise from intricate interactions among genetic, environmental, and epigenetic factors that disrupt immune homeostasis. In recent years, epigenetic mechanisms have been widely explored as critical factors in autoreactivity. Among these modifications, N6-methyladenosine (m6A) RNA methylation stands out as a pivotal post-transcriptional regulator of immune cell function and autoimmune diseases (ADs) progression. This review outlines m6A regulation in immune microenvironments and its dual role in maintaining tolerance and promoting inflammation. This study highlights how m6A regulators, including writers (METTL3\/14), erasers (FTO and ALKBH5), and readers (YTHDF1\u20133 and IGF2BP3), orchestrate immune cell dysfunction across systemic (systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), psoriasis) and organ-specific (multiple sclerosis (MS), inflammatory bowel disease (IBD), type 1 diabetes mellitus (T1DM), and autoimmune thyroid disease (AITD) ADs, revealing disease-specific epitranscriptomic regulatory patterns. Critically, we highlight recent therapeutic breakthroughs targeting m6A regulators, including METTL3 inhibition (STM2457) for Th17-driven MS and RA synovitis, ALKBH5 modulation (ALK-04) to mitigate psoriasis flares and neuroinflammation, FTO-targeting small molecules (Rhein) to prevent RA-associated bone erosion, and IGF2BP3 blockade (triptolide) to suppress RA fibroblast activity. Despite their promise, key challenges persist, including stage-specific effects (early vs. chronic), rare immune subset targeting (MDSCs in AIH), and concerns about the long-term safety of epitranscriptomic drugs. Future studies must address m6A dynamics in immune crosstalk to advance precision medicine strategies, particularly through combinatorial approaches with existing JAK inhibitors or checkpoint modulators.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1887190","type":"journal-article","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T05:38:42Z","timestamp":1783057122000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Epitranscriptomic regulation by m6A in immunity and autoimmune disorders: emerging mechanisms and clinical perspectives"],"prefix":"10.3389","volume":"17","author":[{"given":"Madiha","family":"Maqsood","sequence":"first","affiliation":[{"name":"Department of Microbiology and Parasitology, Anhui Provincial Laboratory of Pathogen Biology, School of Basic Medical Sciences, Anhui Medical University","place":["Hefei, 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China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long","family":"Mei","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Parasitology, Anhui Provincial Laboratory of Pathogen Biology, School of Basic Medical Sciences, Anhui Medical University","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boyang","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Parasitology, Anhui Provincial Laboratory of Pathogen Biology, School of Basic Medical Sciences, Anhui Medical University","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenwen","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Parasitology, Anhui Provincial Laboratory of Pathogen Biology, School of Basic Medical Sciences, Anhui Medical University","place":["Hefei, 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