Adgre5, also known as CD97, is a member of the adhesion G protein-coupled receptors (aGPCRs) family. It plays crucial roles in multiple biological processes. It is involved in immune responses, as it can regulate the homeostasis of spleen dendritic cells (cDC2s) through mechanosensing of red blood cells [2]. It also participates in metabolic regulation, promoting glycolytic metabolism via the mitogen-activated protein kinase (MAPK) pathway in glioblastoma cells [1].

In glioblastoma, CD97 knockdown or knockout significantly reduces the tumor initiation capacity of patient-derived GBM cultures both in vitro and in vivo, indicating its importance in tumorigenesis [1]. In the context of the innate immune response against RNA viruses, CD97-deficient mice are more resistant than wild-type mice to RNA virus infection, as CD97 negatively regulates the innate immune response by promoting RNF125-mediated RIG-I degradation [3]. In macrophages, CD97 knockout THP-1 cells demonstrate that CD97 promotes PPAR-γ expression and decreases LPS-induced NF-κB activation [4].

In conclusion, Adgre5 is essential in immune responses, metabolic regulation, and tumorigenesis. Gene knockout models, such as in glioblastoma, RNA virus-infected mice, and macrophages, have revealed its role in specific disease conditions. These findings contribute to our understanding of the biological functions of Adgre5 and provide potential therapeutic targets for diseases like glioblastoma and RNA virus-related diseases.

References:

1. Ravn-Boess, Niklas, Roy, Nainita, Hattori, Takamitsu, Park, Christopher Y, Placantonakis, Dimitris G. 2023. The expression profile and tumorigenic mechanisms of CD97 (ADGRE5) in glioblastoma render it a targetable vulnerability. In Cell reports, 42, 113374. doi:10.1016/j.celrep.2023.113374. https://pubmed.ncbi.nlm.nih.gov/37938973/

2. Liu, Dan, Duan, Lihui, Rodda, Lauren B, Marson, Alexander, Cyster, Jason G. 2022. CD97 promotes spleen dendritic cell homeostasis through the mechanosensing of red blood cells. In Science (New York, N.Y.), 375, eabi5965. doi:10.1126/science.abi5965. https://pubmed.ncbi.nlm.nih.gov/35143305/

3. Chang, Huasong, Hou, Peili, Wang, Xuefeng, Gao, Yuwei, He, Hongbin. 2023. CD97 negatively regulates the innate immune response against RNA viruses by promoting RNF125-mediated RIG-I degradation. In Cellular & molecular immunology, 20, 1457-1471. doi:10.1038/s41423-023-01103-z. https://pubmed.ncbi.nlm.nih.gov/37978243/

4. Wang, Shuai, Sun, Zewei, Zhao, Wenting, Yan, Hui, Zhu, Jianhua. 2016. CD97/ADGRE5 Inhibits LPS Induced NF-κB Activation through PPAR-γ Upregulation in Macrophages. In Mediators of inflammation, 2016, 1605948. doi:10.1155/2016/1605948. https://pubmed.ncbi.nlm.nih.gov/26997758/