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However, the interplay between microRNAs (miRNAs) and N6\u2010methyladenosine (m6A) modulation in regulating this balance remains poorly understood. Here, a significant reduction in miR\u201031\u20105p levels is observed in the lacrimal glands of rabbit autoimmune dacryoadenitis and the peripheral blood mononuclear cells (PBMCs) of Sj\u00f6gren's syndrome (SS) dry eye patients. Overexpression of miR\u201031\u20105p exhibits preventive and therapeutic effects on rabbit autoimmune dacryoadenitis. Further investigation revealed that miR\u201031\u20105p overexpression significantly restored the M1\/M2 macrophage balance both in vivo and in vitro. Mechanistically, miR\u201031\u20105p directly targets the P2x7 receptor (P2RX7), leading to the inactivation of p38 mitogen\u2010activated protein kinases (MAPK) signaling and reduced expression of M1 markers. Furthermore, methylated RNA immunoprecipitation and luciferase reporter assays demonstrated that fat mass and obesity\u2010associated protein (FTO)\u2010mediated m6A demethylation, which sustains pri\u2010miR\u201031 stability, is responsible for the decreased miR\u201031\u20105p levels in autoimmune dry eye. Notably, PBMC samples from SS dry eye patients further support the link between reduced miR\u201031\u20105p levels and M1 macrophage activation observed in rabbits. Overall, these data highlight the critical role of the FTO\/miR\u201031\u20105p\/P2RX7\/p38 MAPK axis in autoimmune inflammation, suggesting their potential as therapeutic targets for autoimmune dry eye.<\/jats:p>","DOI":"10.1002\/advs.202415341","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T16:03:00Z","timestamp":1741708980000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["M6A Modified miR\u201031\u20105p Suppresses M1 Macrophage Polarization and Autoimmune Dry Eye by Targeting P2RX7"],"prefix":"10.1002","volume":"12","author":[{"given":"Lu","family":"Zhao","sequence":"first","affiliation":[{"name":"Tianjin Key Laboratory of Retinal Functions and Diseases Tianjin Branch of National Clinical Research Center for Ocular Disease Eye Institute and School of Optometry Tianjin Medical University Eye Hospital  Tianjin 300384 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