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However, its metabolic regulation is not well understood. Herein, we identified a macrophage\u2010dependent methionine\u2010S\u2010adenosylmethionine (SAM)\u2010protein arginine methyltransferase 1 (PRMT1)\u2010lactate dehydrogenase A (LDHA)\u2010lactate axis that controls intestinal inflammation through STAT3 regulation. Specifically, SAM promoted STAT3 Y705 phosphorylation and upregulated anti\u2010inflammatory interleukin\u201010 expression in macrophages. Additionally, genetic ablation of PRMT1 in myeloid cells not only impairs STAT3 activation but also exacerbates colitis and promotes inflammation\u2010associated tumorigenesis. Mechanistically, PRMT1 directly methylates LDHA at R268\/R269, thereby enhancing its activity and lactate production. Subsequently, the resulting lactate induces STAT3 lactylation at K709, stabilizing an open conformation that facilitates Y705 phosphorylation. Importantly, disruption of this modification through K709\u2010specific inhibition effectively blocks STAT3 activation and, consequently, exacerbates colitis progression. Overall, this study reveals STAT3 lactylation as a novel post\u2010translational modification that integrates methionine metabolism with glycolytic flux to regulate intestinal inflammation, highlighting the critical role of immunometabolism in colonic inflammation.<\/jats:p>","DOI":"10.1002\/advs.202516577","type":"journal-article","created":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T07:55:05Z","timestamp":1780300505000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["PRMT1\u2010Mediated LDHA Methylation Drives STAT3 Lactylation to Orchestrate Intestinal Inflammation and Tumorigenesis"],"prefix":"10.1002","volume":"13","author":[{"given":"Hui","family":"Wang","sequence":"first","affiliation":[{"name":"School of Basic Medical Sciences Shandong Second Medical University  Weifang Shandong China"},{"name":"Center for Cell Structure and Function, College of Life Sciences Shandong Normal University  Jinan 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