Regulatory role of phosphorylation in NLRP3 inflammasome activation

NLRP3 is a pattern recognition receptor localized in the cytoplasm that belongs to the NOD-like receptor family. Upon activation by a wide range of danger-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs), NLRP3 recruits the adaptor protein ASC and the cysteine protease pro-caspase-1 to form a multiprotein complex called the NLRP3 inflammasome. The primary function of the NLRP3 inflammasome is to maintain homeostasis by facilitating the immune response to remove pathogens and danger signals. However, aberrant activation of the NLRP3 inflammasome also causes a variety of inflammatory diseases.Therefore, NLRP3 inflammasome activation must be precisely regulated. Recently, various kinases and phosphatases have been reported to control the NLRP3 inflammasome activation, suggesting that phosphorylation plays a vital role in regulating the inflammasome activation. In this review, we summarize how various kinases and phosphatases control the NLRP3 inflammasome activation and provide an overview of the regulatory role of phosphorylation in the NLRP3 inflammasome activation. Further, we discuss the potential pharmacologically compounds that target NLRP3-related kinases or phosphatases for the treatment of inflammasome-driven diseases.