Published online Sep 7, 2019. doi: 10.3748/wjg.v25.i33.4796
Peer-review started: May 30, 2019
First decision: July 21, 2019
Revised: July 30, 2019
Accepted: August 7, 2019
Article in press: August 7, 2019
Published online: September 7, 2019
Processing time: 101 Days and 20.9 Hours
Inflammasomes are multiprotein intracellular complexes which are responsible for the activation of inflammatory responses. Among various subtypes of inflammasomes, NLRP3 has been a subject of intensive investigation. NLRP3 is considered to be a sensor of microbial and other danger signals and plays a crucial role in mucosal immune responses, promoting the maturation of proinflammatory cytokines interleukin 1β (IL-1β) and IL-18. NLRP3 inflammasome has been associated with a variety of inflammatory and autoimmune conditions, including inflammatory bowel diseases (IBD). The role of NLRP3 in IBD is not yet fully elucidated as it seems to demonstrate both pathogenic and protective effects. Studies have shown a relationship between genetic variants and mutations in NLRP3 gene with IBD pathogenesis. A complex interaction between the NLRP3 inflammasome and the mucosal immune response has been reported. Activation of the inflammasome is a key function mediated by the innate immune response and in parallel the signaling through IL-1β and IL-18 is implicated in adaptive immunity. Further research is needed to delineate the precise mechanisms of NLRP3 function in regulating immune responses. Targeting NLRP3 inflammasome and its downstream signaling will provide new insights into the development of future therapeutic strategies.
Core tip: NLRP3 inflammasome plays a major role in inflammatory bowel diseases (IBD) pathogenesis through its contribution to chronic inflammatory processes. Abnormal activation of NLRP3 inflammasome has been observed in inflamed tissue of IBD murine models and patients, highlighting its possible pathogenic role in the disease. However, protective effects of NLRP3 function have also been recorded. The pathogenic NLRP3 inflammasome activity in mucosal immune system may be implicated in the aberrant immune responses and in the disruption of intestinal homeostasis that characterizes IBD. Targeting NLRP3 inflammasome and its downstream signaling will provide new insights into the development of future therapeutic strategies.