Role of the NLRP3 inflammasome in autoimmune diseases

Abstract

NOD-like receptor family pyrin domain containing 3 (NLRP3) is an intracellular receptor that senses foreign pathogens and endogenous danger signals. It assembles with apoptosis-associated speck-like protein containing a CARD (ASC) and caspase-1 to form a multimeric protein called the NLRP3 inflammasome. Among its various functions, the NLRP3 inflammasome can induce the release of the pro-inflammatory cytokines interleukin (IL)-1β and IL-18 while also promoting gasdermin D (GSDMD)-mediated pyroptosis. Previous studies have established a vital role for the NLRP3 inflammasome in innate and adaptive immune system as well as its contribution to several autoimmune diseases including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjögren's syndrome (SS), systemic sclerosis (SSc), and ankylosing spondylitis (AS). In this review, we briefly introduce the biological features of the NLRP3 inflammasome and present the mechanisms underlying its activation and regulation. We also summarize recent studies that have reported on the roles of NLRP3 inflammasome in the immune system and several autoimmune diseases, with a focus on therapeutic and clinical applications.

Keywords: Autoimmune disease; Inflammasome; NLRP3.