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Intracranial infection of susceptible mice with the glial-tropic JHM strain of mouse hepatitis virus (JHMV) induces acute encephalomyelitis, followed by an immune-mediated demyelinating disease that mimics many clinical and histologic features of multiple sclerosis (MS). Utilizing an inducible fractalkine receptor (Cx3cr1) promoter-driven Cre-loxP recombinant system, we performed timed ablation of Igf1 in microglia to assess its impact on the central nervous system (CNS) response to JHMV. While the loss of microglial IGF-1 did not impair the control of viral replication, it significantly exacerbated spinal cord demyelination. CyTOF and imaging mass cytometry analysis of spinal cords indicated increased myelin damage was associated with increased accumulation of CD8+Ly6C+ effector T cells and reduced expression of TREM2 that impaired transition into a disease-associated microglia (DAM) phenotype capable of sensing and potentially mitigating myelin damage. Collectively, these findings argue that microglial IGF-1 is a non-redundant coordinator of the CNS immune responses that occur in response to CNS viral infection.<\/jats:p>","DOI":"10.3390\/v18050550","type":"journal-article","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T16:07:26Z","timestamp":1779206846000},"page":"550","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Microglial-Derived IGF-1 Serves as a Regulator for Neuroimmune Homeostasis During Viral-Induced Demyelination"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8786-4191","authenticated-orcid":false,"given":"Vanessa M.","family":"Scarfone","sequence":"first","affiliation":[{"name":"Sue & Bill Gross Stem Cell Research Center, University of California, Irvine, CA 92697, 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