Microglia regulate myelin clearance and cholesterol metabolism after demyelination via interferon regulatory factor 5.

ABSTRACT: Interferon regulatory factor 5 (IRF5) is a transcription factor that plays a role in orchestrating innate immune responses, particularly in response to viral infections. Notably, IRF5 has been identified as a microglia risk gene linked to multiple sclerosis (MS), but its specific role in MS pathogenesis remains unclear. Through the use of Irf5^-/- mice, our study uncovers a non-canonical function of IRF5 in MS recovery. Irf5^-/- mice exhibited increased damage in an experimental autoimmune encephalomyelitis (EAE) model and demonstrated impaired oligodendrocyte recruitment into the lesion core following lysolecithin-induced demyelination. Transcriptomic and lipidomic analyses revealed that IRF5 has a role in microglia-mediated myelin phagocytosis, lipid metabolism, and c

SUBMITTER: Montilla A 

PROVIDER: S-EPMC11947375 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature