ASC plays a role in the priming phase of the immune response to type II collagen in collagen-induced arthritis

Although rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology, the role of IL-1 beta and IL-18 in the pathophysiology of RA has been well established. IL-1 beta and IL-18 are generated via cleavage of their pro-forms in the presence of the apoptosis-associated speck-like protein containing a caspase recruit domain (ASC), a known adaptor protein that activates procaspase-1. As such, we investigated the involvement of ASC in the progression of murine collagen-induced arthritis (CIA) and collagen antibody-induced arthritis (CAIA) using ASC-deficient (ASC(-/-)) and wild-type (ASC(+/+)) mice. Analyses were performed by immunohistochemistry for tissues and ELISA for sera. We observed an increase in the expression of ASC, as well as IL-1 beta and IL-18, in the joints of CIA DBA mice, which indicated that ASC is involved in disease development. Next, we demonstrated that the infiltration of inflammatory cells and cartilage/bone destruction in CIA knee joints were significantly increased in ASC(+/+) mice compared with ASC(-/-) mice. No such differences were noted in ASC(+/+) and ASC(-/-) CAIA mice. In terms of cytokine expression in knee joints, IL-1 beta and IL-18 were depressed in ASC-deficient CIA mice compared with wild-type mice, but were similarly expressed in CAIA joints in both mice groups. Taken together, we can conclude that ASC is involved in the development of CIA and plays a role in the priming phase of the immune response to type II collagen.