FCGR1A

Fc gamma receptor Ia (FCGR1A/CD64), a high-affinity receptor for monomeric IgG, is predominantly expressed on myeloid cells including monocytes, macrophages, and dendritic cells. This transmembrane glycoprotein mediates phagocytosis of immune complexes and antibody-dependent cellular cytotoxicity (ADCC) through SYK kinase-dependent signaling pathways. It interacts with Fc regions of IgG1 and IgG3 subtypes, triggering pro-inflammatory cytokine release (e.g., TNF-α, IL-6) via MAPK and NF-κB activation. Dysregulated FCGR1A signaling is implicated in autoimmune disorders (e.g., rheumatoid arthritis, SLE) and chronic inflammatory conditions. Therapeutic strategies targeting FCGR1A include antagonistic monoclonal antibodies to dampen excessive inflammation and Fc-engineered bispecific antibodies leveraging its potent antigen-presenting cell engagement. Recent phase I trials of FCGR1A-directed CAR macrophages demonstrate potential in solid tumor immunotherapy. Polymorphisms in FCGR1A influence susceptibility to bacterial infections and monoclonal antibody therapeutic efficacy.