Fcgr4, short for Fc receptor, IgG, low affinity IV, is a gene associated with Fcγ receptor-mediated phagocytosis pathway. It plays a role in the immune response, as macrophages expressing Fcgr4 are involved in various immunological processes [2,6]. Genetic models, like KO mouse models, can be valuable for further exploring its functions.

In an established murine ICI myocarditis model (Ctla4+/-Pdcd1-/- mice), there was a marked increase in an inflammatory CCR2+ macrophage subpopulation highly expressing Fcgr4. A similar macrophage population expressing the human homologue of mouse FcgR4 was expanded in patients with ICI myocarditis, suggesting a role for Fcgr4-expressing macrophages in the pathogenesis of this disease [1,5]. In a murine model of macrophage activation syndrome (MAS), miR-136-5p and miR-501-3p targeted Fcgr4, leading to increased phagocytosis by macrophages, indicating its role in MAS-related macrophage hyperactivation [2]. In a study on AMI, animal experiments confirmed the up-regulation of Fcgr4 in AMI mouse myocardial tissues, suggesting its potential as a biomarker for improving cardiac repair and slowing heart failure development post-AMI [3]. In ischemic stroke, Fcgr4 was up-regulated in middle cerebral artery occlusion (MCAO) samples, and single-cell data confirmed its expression in neutrophils, indicating its involvement in IS-related pathways [4].

In conclusion, Fcgr4 is crucial in the immune response, especially in macrophage-related functions. Through gene-knockout mouse models, its role in diseases such as ICI myocarditis, MAS, AMI, and ischemic stroke has been revealed. These findings provide valuable insights into disease pathogenesis and potential therapeutic targets related to Fcgr4.

References:

1. Ma, Pan, Liu, Jing, Qin, Juan, Moslehi, Javid, Lavine, Kory J. 2023. Expansion of Pathogenic Cardiac Macrophages in Immune Checkpoint Inhibitor Myocarditis. In Circulation, 149, 48-66. doi:10.1161/CIRCULATIONAHA.122.062551. https://pubmed.ncbi.nlm.nih.gov/37746718/

2. Varsha, Kontham Kulangara, Yang, Xiaoming, Cannon, Alkeiver S, Nagarkatti, Mitzi, Nagarkatti, Prakash. 2024. Identification of miRNAs that target Fcγ receptor-mediated phagocytosis during macrophage activation syndrome. In Frontiers in immunology, 15, 1355315. doi:10.3389/fimmu.2024.1355315. https://pubmed.ncbi.nlm.nih.gov/38558807/

3. Kong, Xugang, Jin, Guangjun. 2024. Comprehensive analysis of macrophage-associated inflammatory genes in AMI based on bulk combined with single-cell sequencing data. In PeerJ, 12, e17981. doi:10.7717/peerj.17981. https://pubmed.ncbi.nlm.nih.gov/39308815/

4. Qin, Rongxing, Xu, Wei, Qin, Qingchun, Xie, Minshan, Chen, Li. 2025. Identification of NETs-related genes as diagnostic biomarkers in ischemic stroke using RNA sequencing and single-cell analysis. In Mammalian genome : official journal of the International Mammalian Genome Society, , . doi:10.1007/s00335-025-10117-z. https://pubmed.ncbi.nlm.nih.gov/40107980/

5. Ma, Pan, Liu, Jing, Qin, Juan, Moslehi, Javid, Lavine, Kory J. 2023. Expansion of Disease Specific Cardiac Macrophages in Immune Checkpoint Inhibitor Myocarditis. In bioRxiv : the preprint server for biology, , . doi:10.1101/2023.04.28.538426. https://pubmed.ncbi.nlm.nih.gov/37162929/

6. Liu, Zhihao, Hu, Jing, Han, Xingzhi, Zhang, Qun, Qian, Xiaoping. 2025. SLAMF8 regulates Fc receptor-mediated phagocytosis in mouse macrophage cells through PI3K-Akt signaling. In Immunology letters, 273, 106990. doi:10.1016/j.imlet.2025.106990. https://pubmed.ncbi.nlm.nih.gov/39983459/