Fcgr3, the Fc receptor for human immunoglobulin G III, is crucial in linking IgG antibody-mediated immune responses with cellular effector functions [3]. It plays a significant role in host defense, being critical for the phagocytosis of opsonized pathogens by macrophages [4]. Fcgr3-related pathways are involved in various immunological processes, and its study is facilitated by genetic models such as knockout mouse lines [1].

In a cartilage antibody-induced arthritis (CAIA) mouse model, inhibiting or deleting Fcgr3 substantially hindered arthritis development, indicating its essential and sufficient role in CAIA, especially when induced by IgG1 antibodies [2]. In macrophages, knockdown of MafB, which promotes Fcgr3 expression, led to reduced Fcgr3 expression and Fc receptor-mediated phagocytosis, while ectopic expression of Fcgr3 attenuated the reduction in phagocytic activity, highlighting Fcgr3's role in macrophage phagocytosis [4]. In the context of crescentic glomerulonephritis in rats, a novel Fcgr3-related sequence (Fcgr3-rs) was found to interact with the common Fc-γ chain, and its deletion in the Wistar-Kyoto rat was associated with enhanced macrophage activity as it inhibited Fc receptor-mediated phagocytosis and signaling related to Fcgr3 [5].

In summary, Fcgr3 is essential for processes like macrophage phagocytosis in host defense and plays a key role in diseases such as arthritis and crescentic glomerulonephritis. Studies using gene knockout and related models in mice and rats have been instrumental in revealing these functions, providing valuable insights into the role of Fcgr3 in specific biological processes and disease conditions.

References:

1. Bruhns, Pierre, Jönsson, Friederike. . Mouse and human FcR effector functions. In Immunological reviews, 268, 25-51. doi:10.1111/imr.12350. https://pubmed.ncbi.nlm.nih.gov/26497511/

2. Xu, Zhongwei, Moreno-Giró, Àlex, Zhao, Danxia, Lundström, Susanna L, Holmdahl, Rikard. 2024. Fcgr2b and Fcgr3 are the major genetic factors for cartilage antibody-induced arthritis, overriding the effect of Hc encoding complement C5. In European journal of immunology, 54, e2350659. doi:10.1002/eji.202350659. https://pubmed.ncbi.nlm.nih.gov/38314895/

3. Shields, R L, Namenuk, A K, Hong, K, Fox, J A, Presta, L G. 2000. High resolution mapping of the binding site on human IgG1 for Fc gamma RI, Fc gamma RII, Fc gamma RIII, and FcRn and design of IgG1 variants with improved binding to the Fc gamma R. In The Journal of biological chemistry, 276, 6591-604. doi:. https://pubmed.ncbi.nlm.nih.gov/11096108/

4. Nemoto, Takako, Shibata, Yoko, Inoue, Sumito, Nishiwaki, Michiko, Kubota, Isao. 2016. MafB enhances the phagocytic activity of RAW264.7 macrophages by promoting Fcgr3 expression. In Biochemical and biophysical research communications, 482, 375-381. doi:10.1016/j.bbrc.2016.11.070. https://pubmed.ncbi.nlm.nih.gov/27847322/

5. Page, Theresa H, D'Souza, Zelpha, Nakanishi, Satoshi, Cook, H Terence, Behmoaras, Jacques. 2011. Role of novel rat-specific Fc receptor in macrophage activation associated with crescentic glomerulonephritis. In The Journal of biological chemistry, 287, 5710-9. doi:10.1074/jbc.M111.260695. https://pubmed.ncbi.nlm.nih.gov/22184119/