NLRC5, also known as NOD4 or NOD27, is a member of the NLR family. It is a transcriptional activator of MHC class I genes, playing a crucial role in innate and adaptive immune responses, and is also involved in regulating diverse signaling pathways such as NF-κB, type I interferon, and inflammasome signaling pathways [3,4,5,6]. It is highly relevant to inflammation, angiogenesis, immunity, apoptosis, and is associated with many diseases including cancers, CNS disorders, and immune diseases [2,3,4,5]. Genetic models like KO/CKO mouse models are valuable for studying its functions.

NLRC5-deficient mice were protected in hemolytic and inflammatory models, suggesting that NLRC5 can drive inflammatory cell death, PANoptosis, in response to specific ligands like PAMP/heme and heme/cytokine combinations [1]. In endometriosis, inhibition of NLRC5 expression promotes the development of ectopic lesions, upregulates pro-inflammatory factors, and downregulates anti-inflammatory factors, indicating its anti-endometriosis effects through inhibiting ERβ-mediated inflammatory response [7].

In conclusion, NLRC5 is a key regulator in immune-related biological processes. Model-based research, especially using NLRC5 KO/CKO mouse models, has revealed its significance in diseases such as inflammation-related disorders and endometriosis. Understanding NLRC5 provides potential therapeutic targets for these diseases.

References:

1. Sundaram, Balamurugan, Pandian, Nagakannan, Kim, Hee Jin, Vogel, Peter, Kanneganti, Thirumala-Devi. 2024. NLRC5 senses NAD+ depletion, forming a PANoptosome and driving PANoptosis and inflammation. In Cell, 187, 4061-4077.e17. doi:10.1016/j.cell.2024.05.034. https://pubmed.ncbi.nlm.nih.gov/38878777/

2. Tang, Feng, Xu, Yadi, Zhao, Bing. 2020. NLRC5: new cancer buster? In Molecular biology reports, 47, 2265-2277. doi:10.1007/s11033-020-05253-5. https://pubmed.ncbi.nlm.nih.gov/31925644/

3. Wu, Yuting, Shi, Tianlu, Li, Jun. 2019. NLRC5: A paradigm for NLRs in immunological and inflammatory reaction. In Cancer letters, 451, 92-99. doi:10.1016/j.canlet.2019.03.005. https://pubmed.ncbi.nlm.nih.gov/30867141/

4. Zhang, Lu, Jiao, Cui, Liu, Lingjuan, Mao, Dingan, Liu, Liqun. 2021. NLRC5: A Potential Target for Central Nervous System Disorders. In Frontiers in immunology, 12, 704989. doi:10.3389/fimmu.2021.704989. https://pubmed.ncbi.nlm.nih.gov/34220868/

5. Wang, Jie-Quan, Liu, Ya-Ru, Xia, Quan, Xia, Qing-Rong, Li, Jun. 2019. Emerging Roles for NLRC5 in Immune Diseases. In Frontiers in pharmacology, 10, 1352. doi:10.3389/fphar.2019.01352. https://pubmed.ncbi.nlm.nih.gov/31824312/

6. Benkő, Szilvia, Kovács, Elek Gergő, Hezel, Felix, Kufer, Thomas A. 2017. NLRC5 Functions beyond MHC I Regulation-What Do We Know So Far? In Frontiers in immunology, 8, 150. doi:10.3389/fimmu.2017.00150. https://pubmed.ncbi.nlm.nih.gov/28261210/

7. Guo, Bao, Zhu, Haiqing, Xiao, Chengwei, Cao, Yunxia, Zhan, Lei. 2024. NLRC5 exerts anti-endometriosis effects through inhibiting ERβ-mediated inflammatory response. In BMC medicine, 22, 351. doi:10.1186/s12916-024-03571-0. https://pubmed.ncbi.nlm.nih.gov/39218863/