Regulation of the NLRP3 Inflammasome by Posttranslational Modifications

Inflammasomes are important in human health and disease, whereby they control the secretion of IL-1β and IL-18, two potent proinflammatory cytokines that play a key role in inflammatory responses to pathogens and danger signals. Several inflammasomes have been discovered over the past two decades. NLRP3 inflammasome is the best characterized and can be activated by a wide variety of inducers. It is composed of a sensor, NLRP3, an adapter protein, ASC, and an effector enzyme, caspase-1. After activation, caspase-1 mediates the cleavage and secretion of bioactive IL-1β and IL-18 via gasdermin-D pores in the plasma membrane. Aberrant activation of NLRP3 inflammasomes has been implicated in a multitude of human diseases, including inflammatory, autoimmune, and metabolic diseases. Therefore, several mechanisms have evolved to control their activity. In this review, we describe the posttranslational modifications that regulate NLRP3 inflammasome components, including ubiquitination, phosphorylation, and other forms of posttranslational modifications.