The role of NLRP3 inflammasome in the pathogenesis of rheumatic disease

Abstract

Inflammasome is a molecular platform that is formed in the cytosolic compartment to mediate host immune responses to infection and cellular damage. Inflammasome can activate caspase-1, leading to the maturation of two inflammatory cytokines interleukin 1β (IL-1β) and IL-18 and initiation of a proinflammatory form of cell death called pyroptosis. Among various inflammasome complexes, the NLRP3 inflammasome is by far the most studied inflammasome. NLRP3 inflammasome is a key factor in regulating host immune defense against infectious microbes and cellular damage. However, the dysregulated NLRP3 inflammasome activation also participates in the pathogenesis of many human disorders. NLRP3 inflammasome plays an important role in the pathogenesis of rheumatic disease such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), ankylosing spondylitis (AS), Sjögren's syndrome (SS), dermatomyositis/polymyositis (DM/PM), gout, and systemic sclerosis (SSc). For example, NLRP3 inflammasome has been found highly activated in synovial tissues and peripheral blood mononuclear cells from RA patients. In this paper, we will discuss the role of NLRP3 inflammasome in the pathogenesis of rheumatic disease.

Keywords: NLRP3 inflammasome; autoimmunity; drug target; inflammation; rheumatic disease.