Kelli Boyd
Faculty Member
Last active: 3/20/2014

Inflammasome-independent role of apoptosis-associated speck-like protein containing a CARD (ASC) in T cell priming is critical for collagen-induced arthritis.

Ippagunta SK, Brand DD, Luo J, Boyd KL, Calabrese C, Stienstra R, Van de Veerdonk FL, Netea MG, Joosten LA, Lamkanfi M, Kanneganti TD
J Biol Chem. 2010 285 (16): 12454-62

PMID: 20177071 · PMCID: PMC2852983 · DOI:10.1074/jbc.M109.093252

Rheumatoid arthritis is an autoimmune disease with 1% prevalence in the industrialized world. The contributions of the inflammasome components Nlrp3, ASC, and caspase-1 in the pathogenesis of collagen-induced arthritis have not been characterized. Here, we show that ASC(-/-) mice were protected from arthritis, whereas Nlrp3(-/-) and caspase-1(-/-) mice were susceptible to collagen-induced arthritis. Unlike Nlrp3(-/-) and caspase-1(-/-) mice, the production of collagen-specific antibodies was abolished in ASC(-/-) mice. This was due to a significantly reduced antigen-specific activation of lymphocytes by ASC(-/-) dendritic cells. Antigen-induced proliferation of purified ASC(-/-) T cells was restored upon incubation with wild type dendritic cells, but not when cultured with ASC(-/-) dendritic cells. Moreover, direct T cell receptor ligation with CD3 and CD28 antibodies induced a potent proliferation of ASC(-/-) T cells, indicating that ASC is specifically required in dendritic cells for antigen-induced T cell activation. Therefore, ASC fulfills a hitherto unrecognized inflammasome-independent role in dendritic cells that is crucial for T cell priming and the induction of antigen-specific cellular and humoral immunity and the onset of collagen-induced arthritis.

MeSH Terms (17)

Animals Apoptosis Regulatory Proteins Arthritis, Experimental Autoantibodies CARD Signaling Adaptor Proteins Carrier Proteins Caspase 1 Collagen Cytoskeletal Proteins Dendritic Cells Humans Lymphocyte Activation Mice Mice, Inbred C57BL Mice, Knockout NLR Family, Pyrin Domain-Containing 3 Protein T-Lymphocytes

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