Caspase-11 mediates oligodendrocyte cell death and pathogenesis of autoimmune-mediated demyelination

Multiple sclerosis (MS) and its animal model, experimental autoimmune encep halomyelitis (EAE), are inflammatory diseases of the central nervous system (CNS) characterized by localized areas of demyelination. The mechanisms un derlying oligodendrocyte (OLG) injury in MS and EAE remain unknown. Here we show that caspase-11 plays crucial roles in OLG death and pathogenesis in EAE. Caspase-11 and activated caspase-3 were both expressed in OLGs in spin al cord EAE lesions. OLGs from caspase-11-deficient mice were highly resist ant to the cell death induced by cytotoxic cytokines. EAE susceptibility an d cytokine concentrations in the CNS were significantly reduced in caspase- 11-deficient mice. Our findings suggest that OLG death is mediated by a pat hway that involves caspase-11 and -3 and leads to the demyelination observe d in EAE.