Myeloid ZNRF1 suppresses autoimmune demyelination and neuroinflammation by regulating MHC-II-mediated T cell activation.

ABSTRACT: Multiple sclerosis (MS) is an autoimmune and neuroinflammation disease characterized by axonal damage, inflammatory demyelination, and neurodegeneration. However, the precise mechanisms underlying MS pathogenesis remain largely unclear. Here, we identify ZNRF1, an E3 ubiquitin ligase, as a critical regulator of experimental autoimmune encephalomyelitis (EAE), a murine model that recapitulates the autoimmune demyelination features of MS. Mice lacking ZNRF1 exhibit increased susceptibility to EAE progression. Notably, ZNRF1 depletion in peripheral myeloid cells, but not in microglia, leads to enhanced immune cell infiltration into the central nervous system, resulting in demyelination and exacerbated disease severity. The heightened EAE severity in Znrf1-deficient mice is associated with inc

SUBMITTER: Chang YC 

PROVIDER: S-EPMC12542093 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature