CD44 variant isoforms control experimental autoimmune encephalomyelitis by affecting the lifespan of the pathogenic T cells

CD44 variant (CD44v) isoforms play important roles in the development of autoimmune disorders, including colitis and arthritis, but their role in multiple sclerosis (MS) has been explored only to a limited extent. We determined the functional relevance of CD44v isoforms in MS and its animal model, experimental autoimmune encephalomyelitis (EAE). Genetic ablation of CD44v7 and CD44v10 isoforms significantly reduced the clinical EAE burden, as well as the number of inflammatory infiltrates. CD44v7 and CD44v10 expression on both memory T and antigen-presenting cells, participated in the development of adoptive transfer EAE. Significantly reduced mRNA expression of Th1 signature genes was detected in the brains of CD44v10−/− mice compared with those of CD44WT mice. Furthermore, forkhead transcription factor 3 (Foxp3), Bcl-2, and inducible nitric oxide synthase (iNOS) levels were reduced in CD44v10−/− brains, whereas active caspase-3 was elevated. Brain-infiltrating CD4hiCD44v10+ T cells preceded EAE onset and...