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Immunol."],"published-print":{"date-parts":[[2026,3,27]]},"abstract":"<jats:p>\n                    The intestinal epithelium plays a critical role in immune-microbiota interactions, yet its contribution to systemic autoimmunity remains unclear. Here, we identify intestinal epithelial cells (IECs) as initiators of experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS). In both EAE mice and patients with MS, IECs up-regulate antigen presentation pathways and are associated with increased intestinal T helper 17 (T\n                    <jats:sub>H<\/jats:sub>\n                    17) cell accumulation. Epithelial major histocompatibility complex class II (MHC II) was highly expressed during EAE, particularly in the ileum, and its conditional deletion reduced pathogenic T\n                    <jats:sub>H<\/jats:sub>\n                    17 cell generation and disease severity. Using parabiosis and photoconversion models, we demonstrate that T\n                    <jats:sub>H<\/jats:sub>\n                    17 cells induced in the intestinal lamina propria migrate to the spinal cord. Functional coculture assays showed that IEC organoids with cognate myelin oligodendrocyte glycoprotein antigen induce ROR\u03b3t\n                    <jats:sup>+<\/jats:sup>\n                    CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell differentiation in an MHC II\u2013dependent manner. These findings uncover a conserved gut\u2013central nervous system axis in autoimmunity and position epithelial antigen presentation as a key initiator of neuroinflammation.\n                  <\/jats:p>","DOI":"10.1126\/sciimmunol.aec1627","type":"journal-article","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T18:02:47Z","timestamp":1774634567000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":3,"title":["Intestinal epithelial MHC class II induces encephalitogenic CD4 T cells and initiates central nervous system autoimmunity"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6956-2608","authenticated-orcid":true,"given":"Shohei","family":"Suzuki","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, 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