| Acts as the sensor component of the NLRP6 inflammasome, which mediates inflammasome activation in response to various pathogen- associated signals, leading to maturation and secretion of IL1B and IL18 (PubMed:21593405, PubMed:30392956, PubMed:32424362, PubMed:34678144). Inflammasomes are supramolecular complexes that assemble in the cytosol in response to pathogens and other damage- associated signals and play critical roles in innate immunity and inflammation (PubMed:30392956). Acts as a recognition receptor (PRR): recognizes and binds specific pathogens and other damage-associated signals, such as lipoteichoic acid (LTA), a cell-wall component of Gram-positive bacteria, or double stranded RNA (dsRNA) (PubMed:26494172, PubMed:30392956, PubMed:34678144). May also recognize and bind lipopolysaccharide (LPS), a major component of the outer membrane of Gram-negative bacteria; however, LPS is probably not a major activator of the NLRP6 inflammasome (PubMed:34678144). Following LTA- or dsRNA-binding, NLRP6 undergoes liquid-liquid phase separation (LLPS), enhancing multivalent interactions, an essential step for the formation of the NLRP6 inflammasome polymeric complex (PubMed:34678144). The NLRP6 inflammasome acts by promoting recruitment of effector pro-inflammatory caspases (CASP1 and/or CASP4) that catalyze maturation and secretion of IL1B and IL18 in the extracellular milieu (PubMed:30392956). The NLRP6 inflammasome plays a central role in the maintenance of epithelial integrity and host defense against microbial infections in the intestine (PubMed:21565393, PubMed:22763455, PubMed:23696660, PubMed:26638072, PubMed:28445725, PubMed:30392956). Required to restrict infection against Gram-positive bacteria by recognizing lipoteichoic acid (LTA), leading to recruitment of CASP4 and CASP1, and subsequent maturation and secretion of IL1B and IL18 (PubMed:30392956). Involved in intestinal antiviral innate immunity together with DHX15: recognizes and binds viral dsRNA to restrict infection by enteric viruses through the interferon pathway and GSDMD-dependent release of IL18 (PubMed:26494172, PubMed:34678144). Required to prevent infection by the apicomplexan parasite C.tyzzeri in enterocytes by promoting GSDMD-dependent release of IL18 (PubMed:33372132). The NLRP6 inflammasome may also regulate the gut microbiota composition by acting as a sensor of microbiota-associated metabolites to form a PYCARD/ASC-dependent inflammasome for downstream IL18 release and secretion of antimicrobial peptides (PubMed:21565393, PubMed:22763455, PubMed:26638072, PubMed:33617596). Its role in the regulation of the gut microbiota composition is however subject to discussion (PubMed:29281815, PubMed:29281837, PubMed:28801232). Essential for gut mucosal self-renewal and proliferation (PubMed:21593405, PubMed:21543645, PubMed:21565393). Regulate mucus secretion in an inflammasome- and autophagy-dependent manner to prevent invasion by enteric bacteria (PubMed:24581500, PubMed:27339979). During systemic bacterial infections, the NLRP6 inflammasome negatively regulates neutrophil recruitment and neutrophil extracellular traps (NETs) formation (PubMed:22763455, PubMed:30248149, PubMed:33918100, PubMed:33230225). May promote peripheral nerve recovery following injury via an inflammasome-independent mechanism (PubMed:26253422). {Experimental EvidencePubMed:21543645, Experimental EvidencePubMed:21565393, Experimental EvidencePubMed:21593405, Experimental EvidencePubMed:22763455, Experimental EvidencePubMed:23696660, Experimental EvidencePubMed:24581500, Experimental EvidencePubMed:26253422, Experimental EvidencePubMed:26494172, Experimental EvidencePubMed:26638072, Experimental EvidencePubMed:27339979, Experimental EvidencePubMed:28445725, Experimental EvidencePubMed:28801232, Experimental EvidencePubMed:29281815, Experimental EvidencePubMed:29281837, Experimental EvidencePubMed:30248149, Experimental EvidencePubMed:30392956, Experimental EvidencePubMed:32424362, Experimental EvidencePubMed:33230225, Experimental EvidencePubMed:33372132, Experimental EvidencePubMed:33617596, Experimental EvidencePubMed:33918100, Experimental EvidencePubMed:34678144}. |
National and Kapodistrian University of Athens
Department of Biology
Biophysics & Bioinformatics Laboratory