NLRP2, a member of the Nod-like receptor (NLR) family, has a complex role in biology. It may be involved in the innate immune response, with the ability to initiate inflammasome and promote inflammation, yet can also down-regulate inflammatory signals. It is associated with the NF-κB pathway and shows high expression in the placenta, indicating potential functions in the reproductive system [1].

In a mouse model of cystinosis, Nlrp2 deletion led to delayed development of Fanconi syndrome and kidney tissue damage. Ctns-/-Nlrp2-/-animals had less glucosuria, calciuria, lower levels of inflammatory cell infiltration, tubular atrophy, and interstitial fibrosis, suggesting Nlrp2 is a potential target for delaying kidney disease progression in cystinosis [2]. In lung adenocarcinoma cells, NLRP2 silencing promoted cell proliferation and migration by stimulating NF-kB signaling, while in triple-negative breast cancer, NLRP2 re-expression inhibited tumor growth and metastasis, enhancing chemotherapeutic sensitivity [3,4]. In oocytes, Nlrp2-deficient mature adult mice showed slower oocyte development and declining reproductive rates, indicating Nlrp2 is a critical regulator of oocyte quality [5].

In conclusion, NLRP2 has diverse functions. It plays a role in inflammation regulation, and its deletion in mouse models reveals its significance in kidney disease, cancer progression, and female fertility. These model-based studies contribute to understanding the role of NLRP2 in specific disease areas, highlighting its potential as a therapeutic target.

References:

1. Zhang, Tongtong, Xing, Fei, Qu, Mingcui, Yao, Yongchao, Xing, Na. 2023. NLRP2 in health and disease. In Immunology, 171, 170-180. doi:10.1111/imm.13699. https://pubmed.ncbi.nlm.nih.gov/37735978/

2. Rossi, Marianna Nicoletta, Matteo, Valentina, Diomedi-Camassei, Francesca, De Benedetti, Fabrizio, Prencipe, Giusi. 2024. Nlrp2 deletion ameliorates kidney damage in a mouse model of cystinosis. In Frontiers in immunology, 15, 1373224. doi:10.3389/fimmu.2024.1373224. https://pubmed.ncbi.nlm.nih.gov/38633264/

3. Li, Tiantian, Li, Xu, Mao, Rongchen, Jin, Lai, Li, Shengnan. 2022. NLRP2 inhibits cell proliferation and migration by regulating EMT in lung adenocarcinoma cells. In Cell biology international, 46, 588-598. doi:10.1002/cbin.11755. https://pubmed.ncbi.nlm.nih.gov/34957627/

4. Jin, Lai, Li, Tiantian, Hong, Yali, Zhang, Yuheng, Li, Shengnan. 2023. Activation of NLRP2 in Triple-Negative Breast Cancer sensitizes chemotherapeutic therapy through facilitating hnRNPK function. In Biochemical pharmacology, 215, 115703. doi:10.1016/j.bcp.2023.115703. https://pubmed.ncbi.nlm.nih.gov/37499769/

5. Kuchmiy, Anna A, D'Hont, Jinke, Hochepied, Tino, Lamkanfi, Mohamed. 2016. NLRP2 controls age-associated maternal fertility. In The Journal of experimental medicine, 213, 2851-2860. doi:. https://pubmed.ncbi.nlm.nih.gov/27881734/