Ataxin-1 regulates B cell function and the severity of autoimmune experimental encephalomyelitis

Abstract

Significance Over 200 genomic loci have been found associated with the risk of developing multiple sclerosis (MS). Despite this important body of data, limited information exists on the cellular pathways and molecular mechanisms underlying MS genetic complexity. In this study, we report the functional characterization of the ataxin-1 encoding ATXN1 susceptibility locus. Ataxin-1 is a polyglutamine protein that is classically associated with the neurodegenerative disorder spinocerebellar ataxia type 1 (SCA1). Here, we show that ataxin-1 also exerts a protective activity against autoimmune demyelination in a preclinical model of MS. This function is associated with an immunomodulatory role mainly targeting the B cell compartment. Altogether, these findings expand our current knowledge on both MS pathogenesis and ataxin-1 biology.