Cutting Edge: Critical Role for PYCARD/ASC in the Development of Experimental Autoimmune Encephalomyelitis

Abstract

Multiple sclerosis is an autoimmune disease in which self-reactive T cells attack oligodendrocytes that myelinate axons in the CNS. Experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, is dependent on caspase-1; however, the role of Nod-like receptors upstream of caspase-1 is unknown. Danger- and pathogen-associated molecular patterns activate Nod-like receptor 3, which activates caspase-1 through the adaptor protein, apoptosis-associated speck-like protein containing CARD (ASC). We report that the progression of EAE is dependent on ASC and caspase-1 but not Nod-like receptor 3. ASC−/− mice were even more protected from the progression of EAE than were caspase-1−/− mice, suggesting that an inflammasome-independent function of ASC contributes to the progression of EAE. We found that CD4+ T cells deficient in ASC exhibited impaired survival; accordingly, ASC−/− mice had fewer myelin oligodendrocyte glycoprotein–specific T cells in the draining lymph nodes and CNS.