Inflammasome-independent Role of Apoptosis-associated Speck-like Protein Containing a CARD (ASC) in T Cell Priming Is Critical for Collagen-induced Arthritis

Inflammasome-independent role of the apoptosis-associated speck-like protein containing CARD (ASC) in the adjuvant effect of MF59

“…Complexities of the response to adjuvants aside, our data support recent findings in the murine model of collagen-induced arthritis as well as in the development of experimental autoimmune encephalomyelitis that show an inflammasome-independent role for ASC in the induction of various forms of immunity and immunopathology (26,27). There are several molecular mechanisms by which ASC may control the antigen-specific antibody response BMDCs.…”

“…A key underlying feature in the ASC −/− mice was the significantly reduced production of key inflammatory cytokines by BMDCs compared with WT-derived cells after stimulation with MF59. Consistent with a defect in antigenpresenting cells, it has been suggested that antigen-specific activation of T cells by ASC-deficient BMDCs was significantly impaired (26). In line with this notion, after a single immunization with MF59-adjuvanted H5N1 vaccine, we observed a delayed antigen-specific antibody response and significantly lower numbers of CD4 + T cells in the draining lymph nodes in ASC −/− but not NLRP3 −/− or caspase-1 −/− mice in comparison with their WT counterparts.…”

Inflammasome-Dependent and -Independent IL-18 Production Mediates Immunity to the ISCOMATRIX Adjuvant

“…This partial phenotype may support that another inflammasome receptor substitutes for NLRP3 in vivo. However, we cannot rule out the alternative possibility that inflammasome-independent immune cell functions, such as Ag uptake and chemotaxis, might be perturbed in ASC and caspase-1/11 knockout mice (51)(52)(53).…”

PYCARD (PYD and CARD domain containing)

“…Furthermore, antigen-induced proliferation of purified T cells lacking PYCARD [ASC (-/-)] is restored upon incubation with wild type dendritic cells, but not when cultured with ASC (-/-) dendritic cells (Ippagunta et al, 2010). Cell death (apoptosis, pyroptosis, necrosis) PYCARD promotes caspase-mediated inhibition of cellular proliferation, DNA fragmentation and apoptosis via caspases including caspase-2/3/8 and 9 to activate the mitochondrial apoptotic pathway.…”

“…Dysregulated ATP, lipid, urate and glucose metabolism disrupts microtubule polymerization, inflammasome assembly and proinflammatory cytokine production. Tubulin polymerization is critical for mitochondrial transport and inflammasome assembly by allowing for juxtaposition of ASC with NLRP3 in the cytosol (Martinon et al, 2006;Griffith et al, 2009;Ippagunta et al, 2010;Wen et al, 2011;Lu et al, 2012;Wen et al, 2012;Akira et al, 2013;Benetti et al, 2013;Grant and Dixit, 2013;Jourdan et al, 2013;Lee et al, 2013).…”