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The interaction between these systems is complex, and as such, there is the potential for MS therapies to have conflicting effects in different tissues. It is therefore critical that in addition to tissue\u2010specific studies, system\u2010wide effects of potential therapeutic pathways are explored. The circulating protein Gas6 is a promising therapy to promote remyelination in people with multiple sclerosis. Gas6 is a ligand for the TAM family of receptor protein tyrosine kinases that are widely expressed in the immune system and in the CNS, highlighting the potential for multi\u2010system effects as a result of Gas6 treatment. In this study, we demonstrate that global genetic deletion of either Gas6 or the Gas6 receptor Tyro3 results in reduced disease severity following induction of experimental immune encephalomyelitis in mice. The reduction in severity was accompanied by increased expression of both IL\u20104 and IL\u201017A in Tyro3 KO mice lymph node tissue and decreased expression of both cytokines in spinal cord tissues. IL\u20104 is a cytokine known to be protective in inflammatory demyelination in mice. Conversely, the cytokine IL\u201017A is known to be pathological. The overall shift to reduced disease severity highlights the multi\u2010faceted role of TAM receptor signaling in inflammatory demyelination.<\/jats:p>","DOI":"10.1111\/imcb.70054","type":"journal-article","created":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T10:25:20Z","timestamp":1754648720000},"page":"857-870","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Tyro3 deletion is protective in experimental autoimmune encephalomyelitis"],"prefix":"10.1111","volume":"103","author":[{"given":"Michele D","family":"Binder","sequence":"first","affiliation":[{"name":"The Florey Institute of Neuroscience and Mental Health  Parkville VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Asadian","sequence":"additional","affiliation":[{"name":"The Florey Institute of Neuroscience and Mental Health  Parkville VIC 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