NLRP6

Description

The NLRP6 (NLR family pyrin domain containing 6) is a protein-coding gene located on chromosome 11.

NLRP6, short for NOD-like receptor family pyrin domain containing 6, is an intracellular protein that plays a role in the immune system. It is also known as NALP6, PYPAF5, PAN3, and CLR11.4, and is one of 14 pyrin domain containing members of the NOD-like receptor family of pattern recognition receptors. As with several other NOD-like receptors, NLRP6's role in immunity is related to its ability to regulate caspase-1 and NF-κB activity.

NLRP6, also known as NACHT, LRR and PYD domains-containing protein 6, Angiotensin II/vasopressin receptor, or PYRIN-containing APAF1-like protein 5, acts as the sensor component of the NLRP6 inflammasome. This inflammasome is activated in response to various pathogen-associated signals, leading to the maturation and secretion of IL1B and IL18. NLRP6 is a recognition receptor (PRR) that binds specific pathogens and other damage-associated signals, including lipoteichoic acid (LTA) from Gram-positive bacteria and double-stranded RNA (dsRNA). It may also bind lipopolysaccharide (LPS), a component of Gram-negative bacteria, but LPS is likely not a major activator of the NLRP6 inflammasome. Upon LTA or dsRNA binding, NLRP6 undergoes liquid-liquid phase separation (LLPS), which facilitates the formation of the NLRP6 inflammasome polymeric complex. This complex recruits pro-inflammatory caspases (CASP1 and/or CASP4) that process IL1B and IL18, leading to their release and an inflammatory response. The NLRP6 inflammasome is crucial for maintaining epithelial integrity and defending against microbial infections in the intestine. It restricts Gram-positive bacterial infection by recognizing LTA, leading to CASP4 and CASP1 recruitment and IL1B and IL18 maturation and secretion. It also collaborates with DHX15 in antiviral innate immunity, binding viral dsRNA to restrict enteric virus infection via the interferon pathway and GSDMD-dependent IL18 release. NLRP6 prevents infection by the parasite Cryptosporidium in enterocytes by promoting GSDMD-dependent IL18 release. The NLRP6 inflammasome may regulate gut microbiota composition by sensing microbiota-associated metabolites, forming a PYCARD/ASC-dependent inflammasome for IL18 release and antimicrobial peptide secretion. NLRP6 is essential for gut mucosal self-renewal and proliferation. It regulates mucus secretion in an inflammasome- and autophagy-dependent manner to prevent enteric bacteria invasion. During systemic bacterial infections, the NLRP6 inflammasome negatively regulates neutrophil recruitment and NETs formation. It may also promote peripheral nerve recovery following injury via an inflammasome-independent mechanism.

NLRP6 is also known as AVR, CLR11.4, NALP6, NAVR, NAVR/AVR, PAN3, PYPAF5.

Associated Diseases

WES Whole Exome Sequencing