NLRP3
a cytosolic pattern recognition receptor and scaffolding protein that plays a crucial role in innate immunity and inflammation. Crucial for the formation and activation of inflammasomes. In response to pathogens and other damage-associated signals, initiates the formation of the inflammasome polymeric complex, made of NLRP3, PYCARD and CASP1 (and possibly CASP4 and CASP5). Recruitment and activation of CASP1 to the inflammasome promotes the proteolytic processing, maturation and secretion of IL1B, IL18 and HMGB1, stimulating inflammatory responses. Interaction with MEFV leads to its degradation by autophagy, preventing excessive IL1B- and IL18-mediated inflammation. Inflammasomes can also induce pyroptosis, an inflammatory form of programmed cell death. Activating stimuli include extracellular ATP, reactive oxygen species, K(+) efflux, amyloid-beta fibers, cytosolic dsRNA, environmental or industrial particles and nanoparticles, etc. Activation in presence of cytosolic dsRNA is mediated by DHX33. Independently of inflammasome activation, regulates the differentiation of T helper 2 (Th2) cells. During Th2 differentiation, required for optimal IRF4 binding to IL4 promoter and for IRF4-dependent IL4 transcription. Involved in the regulation of IL4, IL5, and IL13 production. May function as an inducer of apoptosis. Interacts selectively with PYCARD and this complex may function as an upstream activator of NF-kappa-B signaling. Predominantly expressed in macrophages. Also expressed in dendritic cells, B- and T-cells, and LPS-treated granulocytes, but not in resting cells. Expressed weakly in monocytes and in oral, esophageal and ectocervical mucosa, Hassall's corpuscles in the thymus, the stratified epithelium covering the bladder and ureter, lung epithelial cells, chondrocytes, and in resting osteoblasts. 6 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.