NLRP2 proteins

NLRPs (acronym for: NACHT, LRR and PYD domains-containing protein), together with the NOD1 and NOD2 proteins, are members of the NLR(Nod-like receptor) protein family and play a major role in innate immunity as pathogen recognition receptors (PPRs). Like the NOD proteins, NLRPs are exclusively expressed cytoplasmically. In humans, all NLRPs (they all contain a pyrin domain) are encoded by a common gene family. NLRPs are characterized by their ability to activate the inflammasome, a multi-protein complex. Activation of the inflammasome leads to the expression of caspases, enzymes that process and activate inactive interleukin-1beta and interleukin-18 and can thus initiate an inflammatory cascade.

NLRP2 is a cytosolic protein that in humans is encoded by the NLRP2 gene located on chromosome 19q13.42. Like other NLRPs, NLRP2 is one of the key mediators of programmed cell death.

An association between rheumatoid arthritis and polymorphisms in the NLRP2 gene was found in a Chinese Han population (Yang XL et al. 2015).

Human astrocytes, neurons, and microglia express NLRP2 after CNS injury. Injury results in activation of the inflammasome, with expression of caspase-1, which in turn processes inactive interleukin-1beta and interleukin-18, initiating an inflammatory cascade (Minkiewicz J et al. 2013). Therapeutic measures can possibly be derived from this.

During pregnancy, the fetal extravillous trophoblasts (EVT) play a key role in the regulation of the maternal T cell and NK cell response. NLRP2 is markedly expressed in fetal extravillous trophoblasts but not in maternal decidual stromal cells. Apparently, this NLR plays a prominent role in the formulation of unwanted antifetal immune responses.

The fundamental importance of NLRP2 for the immunocompetence of a human organism is demonstrated by various polymorphisms of the coding gene. polymorphisms of the coding NLRP2 gene, which are prognostic factors for the acceptance of a stem cell transplant (Granell M et al.(2008)

1. Granell M et al(2008) Common variants in NLRP2 and NLRP3 genes are strong prognostic factors for the outcome of HLA-identical sibling allogeneic stem cell transplantation. Blood 112:4337-4342.
2. Minkiewicz J et al.(2013) Human astrocytes express a novel NLRP2 inflammasome.Glia 61:1113-1121.
3. Tilburgs T et al (2017) NLRP2 is a suppressor of NF-ƙB signaling and HLA-C expression in human trophoblasts. Biol Reprod 96:831-842.
4. Yang XL et al (2015) Association of polymorphisms in SPARC and NLRP2 genes with rheumatoid arthritis in a Chinese Han population. Mod Rheumatol 25:67-71.
5. Yang CA et al (2015) Inflammasomes and human autoimmunity: A comprehensive review. J Autoimmune 61:1-8.