Low affinity immunoglobulin gamma Fc region receptor IV (FcγRIV) (FcγRIV)

Murine FcγRIV (Low affinity immunoglobulin gamma Fc region receptor IV) is a critical activating receptor expressed on myeloid cells, including neutrophils, monocytes, and macrophages (UniProt P0C0L3). It is distinguished by its high affinity for IgG2a and IgG2b immune complexes, making it a primary mediator of antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis (ADCP) in mice (Nimmerjahn & Ravetch, 2005). Although it lacks a direct human ortholog, it is functionally analogous to human FcγRIIIa (CD16a) and plays a pivotal role in bridging the adaptive and innate immune systems. In preclinical models, FcγRIV is essential for the therapeutic efficacy of many monoclonal antibodies, particularly those of the IgG2a subclass, which are used to target tumors or pathogens. Conversely, its dysregulation is implicated in the pathogenesis of autoimmune and inflammatory diseases, such as rheumatoid arthritis and systemic lupus erythematosus (Hirano et al., 2007). Targeting FcγRIV or its downstream signaling components offers a strategy to modulate immune responses in various disease states. Understanding its biology is crucial for the translation of murine experimental data to human clinical development.

Other names

Fcgr4CD16-2FcgammaRIV4833442P21Rik

FcγRIV is an activating receptor that requires association with the ITAM-bearing Fc receptor gamma chain (FcRγ) for surface expression and signaling. Upon binding to the Fc portion of IgG2a or IgG2b antibodies, it induces phosphorylation of ITAM motifs by Src-family kinases, recruiting Syk kinase and activating downstream pathways like PLCγ and MAPK. This signaling cascade triggers effector functions including antibody-dependent cellular cytotoxicity (ADCC), phagocytosis, and the release of pro-inflammatory cytokines and chemoattractants.