Multiple sclerosis (MS) is an autoimmune disease in which myelin-reactive CD4+
T cells infiltrate the CNS and induce demyelinating disease (1
). Experimental autoimmune encephalomyelitis (EAE) serves as an animal model of MS, and is induced by immunization with a peptide from myelin oligodendrocyte glycoprotein (MOG) emulsified in adjuvant. The infiltration of MOG-specific T cells and other inflammatory cells into the CNS is critical for the development of EAE (2
NOD-like receptors (NLRs) are a recently discovered family of intracellular receptors that sense danger- and pathogen-associated molecular patterns. Members of the NLR family form a caspase-1 activating multiprotein complex, termed inflammasomes (3
). Activation of caspase-1 mediates the proteolytic maturation of the cytokines IL-1β and IL-18. Genetic studies in mice suggest that at least four inflammasomes of distinct composition are formed in vivo in a stimulus-dependent manner: the NLRC4 inflammasome, the NLRP1 inflammasome, the NLRP3 inflammasome, and a fourth inflammasome, for which the NLR protein is unknown, triggered by Francisella tularensis
). In addition to these NLRs, the HIN-200 protein absent in melanoma 2 (AIM2) was recently shown to trigger caspase-1 activation in response to cytoplasmic double-stranded DNA (dsDNA) (8
). The bipartite adaptor protein ASC plays a role in the interaction between NLRs/AIM2 and caspase-1 in each of these inflammasome complexes.
The essential role of NLRs in the immune system has led to several studies exploring the role of NLRs in host defense and autoimmune diseases. For example, single amino acid mutations which result in uncontrolled NLRP3 activation causes an autoinflammatory disorder termed cryopyrin-associated periodic syndromes (12
). Additionally, caspase-1 activation (13
) and IL-1 signaling (14
) are important in the progression of EAE, but the role of NLRP3 and the central inflammasome component ASC in the progression of EAE has not been examined.
In this study we show that ASC, but not NLRP3, is involved in the progression of EAE. We also demonstrate that the deficiency in ASC does not affect MOG-specific T cell proliferation or cytokine production in the periphery. However, ASC plays a role in the peripheral survival of mature CD4+ T cells. Therefore, ASC−/− mice have reduced numbers of MOG-specific T cells in the lymph node and CNS resulting in protection from EAE.