Fpr2, also known as formyl peptide receptor 2 or ALX/FPR2, is a seven-transmembrane G-protein coupled receptor. It plays a crucial role in sensing bacteria, modulating immune responses, and is involved in various signaling pathways related to inflammation regulation, tissue homeostasis, and metabolic signaling [2,3]. It binds to ligands from different sources and is expressed in multiple cell types such as myeloid cells, epithelial cells, endothelial cells, neurons, and hepatocytes [3].

In the context of disease, genetic ablation models have provided insights. In Fpr2-/-mice, exacerbated alcohol-associated liver disease was observed, with more severe liver injury, inflammation, and compromised regeneration, along with abnormal immune responses [4]. In a murine colitis model, genetic ablation of the Fpr2 gene abolished the enhancement of macrophage-mediated efferocytosis, anti-colitis activity, and LC3-associated phagocytosis induced by columbamine, suggesting Fpr2 as a potential target for alleviating intestinal inflammation [1]. In streptococcal toxic shock-like syndrome, Fpr2-/-mice had a reduced inflammatory response, decreased bacterial load, and increased neutrophil recruitment compared to wild-type mice, indicating Fpr2 exacerbates the disease by impairing neutrophil recruitment [5].

In conclusion, Fpr2 is essential in regulating immune responses, tissue homeostasis, and metabolic processes. Gene knockout mouse models have revealed its significant roles in diseases like alcohol-associated liver disease, colitis, and streptococcal toxic shock-like syndrome. These findings highlight Fpr2 as a potential therapeutic target for treating related diseases [1,4,5].

References:

1. Wu, Ming-Yue, Ge, Yun-Jun, Wang, Er-Jin, Ye, Richard D, Lu, Jia-Hong. 2023. Enhancement of efferocytosis through biased FPR2 signaling attenuates intestinal inflammation. In EMBO molecular medicine, 15, e17815. doi:10.15252/emmm.202317815. https://pubmed.ncbi.nlm.nih.gov/37994307/

2. Alessi, Marie-Christine, Cenac, Nicolas, Si-Tahar, Mustapha, Riteau, Béatrice. 2017. FPR2: A Novel Promising Target for the Treatment of Influenza. In Frontiers in microbiology, 8, 1719. doi:10.3389/fmicb.2017.01719. https://pubmed.ncbi.nlm.nih.gov/28928730/

3. Chen, Keqiang, Gong, Wanghua, Huang, Jiaqiang, Yoshimura, Teizo, Ming Wang, Ji. 2023. Developmental and homeostatic signaling transmitted by the G-protein coupled receptor FPR2. In International immunopharmacology, 118, 110052. doi:10.1016/j.intimp.2023.110052. https://pubmed.ncbi.nlm.nih.gov/37003185/

4. Hardesty, Josiah E, Warner, Jeffrey B, Song, Ying L, Warner, Dennis R, Kirpich, Irina A. 2023. Fpr2-/- Mice Developed Exacerbated Alcohol-Associated Liver Disease. In Biology, 12, . doi:10.3390/biology12050639. https://pubmed.ncbi.nlm.nih.gov/37237453/

5. Ni, Chengpei, Gao, Song, Li, Xudong, Kong, Decong, Jiang, Yongqiang. 2023. Fpr2 exacerbates Streptococcus suis-induced streptococcal toxic shock-like syndrome via attenuation of neutrophil recruitment. In Frontiers in immunology, 14, 1094331. doi:10.3389/fimmu.2023.1094331. https://pubmed.ncbi.nlm.nih.gov/36776849/