NLRP12

Official Full Name

NLR family pyrin domain containing 12

Organism

Homo sapiens

GeneID

91662

Background

This gene encodes a member of the CATERPILLER family of cytoplasmic proteins. The encoded protein, which contains an N-terminal pyrin domain, a NACHT domain, a NACHT-associated domain, and a C-terminus leucine-rich repeat region, functions as an attenuating factor of inflammation by suppressing inflammatory responses in activated monocytes. Mutations in this gene cause familial cold autoinflammatory syndrome type 2. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2013]

Synonyms

RNO; PAN6; RNO2; FCAS2; NALP12; PYPAF7; CLR19.3;

Cat.No.	Product Name	Price

Cat.No.	Product Name	Price

Cat.No.	Product Name	Price

Cat.No.	Product Name	Price

Detailed Information

NLRP12 (also known as RNO, PYPAF7 and Monaroh-1) is one of the NLRs proteins and contains an N-terminal PYD, an NBD and a C-terminal LRR region, which is an intracellular protein. Human NLRP12 is significantly expressed in bone marrow cells such as neutrophils, eosinophils, monocytes, macrophages, and immunodendritic cells, and is down-regulated under the action of pathogens, pathogen products, and inflammatory cytokines. Similar to humans, murine NLRP12 is expressed in bone marrow, spleen and neutrophils and dendritic cells. NLRP12 is also expressed in the small intestine, cecum, colon, and mesenteric lymph node (MLN). The cells expressing the highest NLRP12 mRNA are neutrophils and T cells, followed by dendritic cells and macrophages.

NLRP12 is a recently identified member of the NLR family that is capable of detecting mutations in NLRP12 in some patients that cause periodic fever and characteristic dermatitis in patients. Previous in vitro experiments have suggested that NLRP12 is a negative regulator of the TLR signaling pathway, and recent studies have linked NLRP12 to the negative regulation of inflammatory responses. Although these studies together reveal the role of NLRP12 in innate immune cells, its effects on T cells are currently unclear. Studies have shown that wild-type mice and NLRP12-/- mice are combined with MOG polypeptide and CFA adjuvant. One month later, the spleen T cells of the stimulated mouse are isolated for secondary activation. The results showed that mutant mice were able to express higher IFN-gamma, IL-17 and TNF-a relative to wild-type mice, suggesting a negative regulation of NLRP12-/- on T cell activation.

Nlrp12 Figure 1. NLRP12 regulates microbial diversity and maintains intestinal homeostasis. (Lau, M. F., et al. 2017)

NLRP12 and Signal Pathway

NLRP12 negatively regulates both classical and non-canonical NF-kB signaling pathways via the kinases IRAK1 and NIK in vitro. Studies have shown that NLRP12 has only a weak regulation effect on the classical NF-kB signaling pathway and does not affect the expression of IL-1β and TNF-α in the early stage of enteritis. Studies have also shown that the non-canonical NF-kB signaling pathway can influence the classical NF-kB signaling pathway through IKKα- and TRAF3-dependent mechanisms. Therefore, NLRP12 is an important regulatory point of the non-canonical NF-kB signaling pathway.

Reports indicate that when NLRP12 is overexpressed in non-immune cells, NLRP12 and ASC act together to activate NF-kB and caspase-1, whereas caspase-1 is required for processing and maturation of the inflammatory factors IL-1β and IL-18. IL-1β is produced by cells of the innate immune system (e.g., macrophages, dendritic cells, monocytes) and non-immune cells such as epithelial cells, and its secretion can increase the inflammatory effect. The secretion of IL-1β in epithelial cells and lamina propria of macrophages and dendritic cells was significantly increased in patients with inflammatory bowel disease (IBD). Caspase-1, which regulates IL-1β and IL-18 secretion, has also been shown to be a central regulator of DSS-induced colitis. It can be speculated that NLRP12 may affect the development of IBD by activating NF-kB and caspase-1.

Nlrp12 and Inflammatory Bowel Disease (IBD)

Many studies have shown that the levels of inflammatory factors and chemical factors in NLRP12-/- mice are significantly increased, so NLRP12 may play an important role in the development of IBD.

Studies have shown that in addition to being a pattern recognition receptors (PRRs) that mediate inflammatory responses, NLRP12 is involved in other physiological and pathological processes and functions as a non-inflammatory mediated function. Studies have shown that NLRP12 can promote dendritic cells and neutrophils in the mouse contact hypersensitivity (CHS) from peripheral migration to draining lymph nodes, and do not respond to chemokines in vitro, nor affect Dendritic cells present antigen. Under TLR stimulation, NLRP12 does not significantly affect the production of proinflammatory factors such as IL-1β and TNF-α in dendritic cells. These indicate that NLRP12 does not affect inflammatory function and does not affect TNF-α in CHS, but the mechanism remains unclear.

References:

Lau, M. F. , & Dombrowski, Y. . (2017). The innate immune receptor nlrp12 maintains intestinal homeostasis by regulating microbiome diversity. Cellular & Molecular Immunology.
Zaki, M. H. , Man, S. M. , Vogel, P. , Lamkanfi, M. , & Kanneganti, T. D. . (2014). Salmonella exploits nlrp12-dependent innate immune signaling to suppress host defenses during infection. Proceedings of the National Academy of Sciences, 111(1), 385-390.
Shen, M. , Tang, L. , Shi, X. , Zeng, X. , & Yao, Q. . (2016). Nlrp12 autoinflammatory disease: a chinese case series and literature review. Clinical Rheumatology, 36(7), 1-7.

Quick Inquiry

Interested in learning more?

Contact us today for a free consultation with the scientific team and discover how Creative Biogene can be a valuable resource and partner for your organization.

Request a quote today!

Inquiry