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Stereo\u2010seq was performed on\n Ap1m2<\/jats:italic>\n \u2212\/\u2212<\/jats:sup>\n and\n Ap1m2<\/jats:italic>\n \u2212\/\u2212<\/jats:sup>\n ::\n Tnfr1<\/jats:italic>\n \u2212\/\u2212<\/jats:sup>\n mouse samples to investigate the regulatory role of Tnfr1 signaling in the pathogenesis of\n Ap1m2<\/jats:italic>\n deficiency\u2013caused intestinal inflammation. Superrevolution imaging and clathrin\u2010coated vesicle enrichment were used to explore the molecular mechanism by which AP1M2 suppresses NF\u2010\u03baB activation and chemokine production.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Ap1m2<\/jats:italic>\n \u2212\/\u2212<\/jats:sup>\n mice exhibited elevated chemokine production in serum and spontaneously developed intestinal inflammation, which phenocopies the patient with the\n AP1M2<\/jats:italic>\n variant. Mechanistically, the deficiency of intestinal epithelial specific\n AP1M2<\/jats:italic>\n expression resulted in accumulation of TNFR1\u2010signaling downstream proteins, including RIPK1, TBK1, IKK\u03b1\/\u03b2, and NEMO, leading to enhanced NF\u2010\u03baB activation and subsequent chemokine overproduction.\n Tnfr1<\/jats:italic>\n knockout rescued gastrointestinal inflammation induced by\n Ap1m2<\/jats:italic>\n deficiency through suppressing NF\u2010\u03baB activation and chemokine production.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n This study identifies the deficiency of\n AP1M2<\/jats:italic>\n as the cause of a new autoinflammatory disease with colitis and highlights the critical function of AP\u20101 in suppressing NF\u2010\u03baB activation and chemokine production.\n <\/jats:p>\n \n \n \n image<\/jats:alt-text>\n <\/jats:graphic>\n <\/jats:boxed-text>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/art.70038","type":"journal-article","created":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T09:49:38Z","timestamp":1766742578000},"page":"1306-1317","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Deficiency of\n \n AP1M2<\/i>\n <\/scp>\n Causes a New Autoinflammatory Disease With Colitis"],"prefix":"10.1002","volume":"78","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4238-7293","authenticated-orcid":false,"given":"Taijie","family":"Jin","sequence":"first","affiliation":[{"name":"Department of Rheumatology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine Liangzhu Laboratory of Zhejiang University Hangzhou China"},{"name":"Department of Rheumatology, The Second Affiliated Hospital Zhejiang University School of Medicine Hangzhou 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