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

Multiple sclerosis (MS) is an autoimmune disease in which self-reactive T cells attack oligodendrocytes that myelinate axons in the central nervous system. Experimental autoimmune encephalomyelitis (EAE), an animal model of MS, is dependent on caspase-1, but the role of NLRs upstream of caspase-1 is unknown. Danger- and pathogen-associated molecular patterns (DAMPs and PAMPs, respectively) activate Nod-like receptor 3 (NLRP3) which then activates caspase-1 through the adaptor protein, ASC. We report that the progression of EAE is dependent on ASC and caspase-1, but not NLRP3. ASC −/− mice were even more protected from the progression of EAE than caspase-1 −/− mice, suggesting an inflammasome-independent function of ASC which contributes to the progression of EAE. We found that CD4 + T cells deficient in ASC exhibited impaired survival and accordingly ASC −/− mice had less MOG-specific T cells in both the draining lymph nodes and CNS.