Fcgr3, the Fc receptor for human immunoglobulin G III, is crucial in linking IgG antibody-mediated immune responses to cellular effector functions. It plays a significant role in host defense, especially in the phagocytosis of opsonized pathogens by macrophages. Fc-FcγR interactions, where Fcgr3 is involved, are essential for the activity of tumour-targeting antibodies, influencing cancer immunotherapies [1,2,4].

In a cartilage antibody-induced arthritis (CAIA) mouse model, inhibiting or deleting Fcgr3 substantially hindered arthritis development. When using an IgG1 arthritogenic cocktail, joint inflammation was promptly initiated in Fcgr2b-mice but not in Fcgr3-mice, suggesting Fcgr3 is essential and sufficient for CAIA development, particularly when induced by IgG1 antibodies [3]. In macrophage cell-line studies, knockdown of MafB, which promotes Fcgr3 expression, led to reduced Fcgr3 expression and Fc receptor-mediated phagocytosis, and the reduced phagocytic activity was attenuated by ectopic expression of Fcgr3 [5].

In conclusion, Fcgr3 is essential for functions like antibody-mediated cellular effector responses, host defense, and phagocytosis. Gene knockout mouse models, such as those in CAIA and macrophage cell-line studies, have revealed its key role in arthritis development and macrophage phagocytic activity, providing valuable insights into related disease mechanisms.