Fc gamma receptors and neonatal Fc receptor (FcγRs and FcRn)

Fc gamma receptors (FcγRs) and the neonatal Fc receptor (FcRn) are the primary receptors responsible for mediating the biological effects and homeostasis of immunoglobulin G (IgG). FcγRs, including FcγRI (CD64), FcγRII (CD32), and FcγRIII (CD16), are expressed on various immune cells and trigger effector functions such as phagocytosis, antibody-dependent cellular cytotoxicity (ADCC), and cytokine release upon binding to the Fc region of IgG [1.2.2, 1.3.3]. In contrast, FcRn is a non-classical MHC class I-like receptor that regulates the half-life of IgG and albumin by protecting them from lysosomal degradation through a pH-dependent recycling pathway [1.1.1, 1.3.2]. These receptors play critical roles in both health and disease; FcγRs are essential for clearing pathogens and tumor cells but can also drive tissue damage in autoimmune conditions, while FcRn maintains high levels of both protective and pathogenic IgG [1.1.3, 1.2.4]. Therapeutic strategies targeting these receptors include FcRn inhibitors (e.g., efgartigimod) to accelerate the clearance of autoantibodies in diseases like myasthenia gravis, and Fc-engineered monoclonal antibodies designed to enhance or inhibit FcγR-mediated effector functions for cancer or inflammatory treatments [1.1.1, 1.2.5].

Other names

IgG receptorsFc receptors for IgGBrambell receptorCD64CD32CD16FCGRT

FcRn inhibitors block the interaction between FcRn and the Fc region of IgG, preventing the pH-dependent recycling of IgG and leading to its lysosomal degradation, which reduces circulating levels of pathogenic autoantibodies [1.1.1, 1.1.3]. Drugs targeting Fc gamma receptors (FcγRs) modulate immune effector functions such as antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and cytokine release by binding to activating (e.g., FcγRIIIa) or inhibitory (e.g., FcγRIIb) receptors [1.2.2, 1.3.3].