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Transl. Med."],"published-print":{"date-parts":[[2026,7,15]]},"abstract":"<jats:p>\n                    Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) that results from oligodendrocyte loss and multifocal demyelination of the CNS white matter. Current therapies can suppress the progression of CNS inflammation but do not actively promote tissue repair. Nanoparticles (NPs) coated with CNS-specific peptide\u2013major histocompatibility complex class II (pMHCII) molecules can alleviate disability in mice with experimental autoimmune encephalomyelitis (EAE) by triggering the formation, expansion, and recruitment of antigen-specific type 1 regulatory CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells (Tr1 cells). By investigating the effects of pMHCII-NP therapy on focal demyelinated lesions in the spinal cord induced by lysolecithin and sustained by chronic autoimmune encephalitogenic insults, here, we show that CNS antigen\u2013specific Tr1 cells promote oligodendrogenesis, the preservation of axon caliber, and remyelination. Cell-specific deletion of\n                    <jats:italic toggle=\"yes\">amphiregulin<\/jats:italic>\n                    (\n                    <jats:italic toggle=\"yes\">Areg<\/jats:italic>\n                    ) in T cells or of the\n                    <jats:italic toggle=\"yes\">epidermal growth factor receptor<\/jats:italic>\n                    (\n                    <jats:italic toggle=\"yes\">Egfr<\/jats:italic>\n                    ) in oligodendrocytes abrogated these therapeutic outcomes. Oligodendrocyte-specific deletion of\n                    <jats:italic toggle=\"yes\">Egfr<\/jats:italic>\n                    did not impair the pharmacodynamic or anti-inflammatory effects of pMHCII-NP treatment. These findings indicate that the oligodendrocyte-mediated therapeutic effects of pMHCII-NP treatment are dissociated from the anti-inflammatory properties of Tr1 cells; instead, they involve Tr1 cell\u2013derived Areg to activate oligodendrocytes in an EGFR-dependent manner. Together, these results indicate that antigen-specific regulatory T cells can promote oligodendrogenesis and highlight the amphiregulin-oligodendrocyte EGFR pathway as a target for therapeutic intervention in MS.\n                  <\/jats:p>","DOI":"10.1126\/scitranslmed.aef2269","type":"journal-article","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T17:59:07Z","timestamp":1784138347000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Murine autoantigen-specific type 1 regulatory T cells promote oligodendrogenesis through amphiregulin-EGFR signaling"],"prefix":"10.1126","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0844-1615","authenticated-orcid":true,"given":"Robert","family":"Clarke","sequence":"first","affiliation":[{"name":"Department of Microbiology, Immunology, and Infectious Diseases, Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, 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