NLRP3 inflammasome activation mechanism and its role in autoimmune liver disease
Yanling Guan, Yiyue Gu, Hao Li, Bo Liang, Chenchen Han, Yu Zhang, Qian Liu, Wei Wei, Yang Ma
Abstract
The NLRP3 inflammasome is a multiprotein binding compound comprising NLRP3, connector protein ASC, and effector protein pro-caspase-1. When the NLRP3 inflammasome senses a danger signal from the host or pathogen, activated caspase-1 cleaves the precursors of interleukin (IL)-1β and IL-18 into mature proinflammatory cytokines, simultaneously causing lysis via the pore-forming protein gasdermin D. This induction of cell inflammatory pyroptosis suggests that it is a key process in the innate immune response to pathogens or cellular stress. Recent studies have shown that NLRP3 inflammasome also plays an important role in regulating autoimmune liver diseases, including autoimmune hepatitis, primary biliary cholangitis, and primary sclerosclerotic cholangitis. In this review, we summarize the structure, activation and modulation of the NLRP3 inflammasome, highlight the progress in research on the role of NLRP3 inflammasome in the occurrence and development of autoimmune liver diseases, and discuss potential strategies for targeting the NLRP3 inflammasome in the treatment of autoimmune liver diseases.