Astrocytic-OTUD7B ameliorates murine experimental autoimmune encephalomyelitis by stabilizing glial fibrillary acidic protein and preventing inflammation.

ABSTRACT: Astrocytes are central to the pathogenesis of multiple sclerosis (MS); however, their regulation by post-translational ubiquitination and deubiquitination is unresolved. This study shows that the deubiquitinating enzyme OTUD7B in astrocytes protects against murine experimental autoimmune encephalomyelitis (EAE), a model of MS, by limiting neuroinflammation. RNA-sequencing of isolated astrocytes and spatial transcriptomics show that in EAE, OTUD7B downregulates chemokine expression in astrocytes of inflammatory lesions, which is associated with reduced recruitment of encephalitogenic CD4⁺ T cells. Furthermore, OTUD7B is necessary for glial fibrillary acidic protein (GFAP) expression of astrocytes bordering inflammatory lesions. Mechanistically, OTUD7B (i) restricts TNF-induced ch

SUBMITTER: Harit K 

PROVIDER: S-EPMC12537900 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature