Fc receptor (FcR) (FcR)

Fc receptors (FcRs) are a diverse family of cell surface glycoproteins that bind the fragment crystallizable (Fc) region of immunoglobulins, serving as a critical bridge between the humoral and cellular branches of the immune system [1, 5]. They are expressed on various immune cells, including natural killer (NK) cells, macrophages, neutrophils, and B cells, where they mediate essential effector functions such as antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and the release of inflammatory mediators [4, 6, 9]. A key member of this family is the neonatal Fc receptor (FcRn), which regulates the half-life of IgG antibodies and albumin by protecting them from lysosomal degradation [1, 10]. In therapeutic contexts, Fc receptors are targeted to treat autoimmune diseases by accelerating the clearance of pathogenic autoantibodies via FcRn inhibition or to enhance the efficacy of anti-cancer monoclonal antibodies by optimizing their interaction with activating Fc gamma receptors (FcγRs) [3, 15]. Conversely, targeting the high-affinity IgE receptor (FcεRI) is a primary strategy for managing allergic disorders [8, 13]. Safety considerations for Fc receptor-targeted biologics include the risk of infection due to reduced systemic IgG levels and potential infusion-related reactions [11, 16].

Other names

Fragment crystallizable receptorCD16CD32CD64CD23CD89Neonatal Fc receptorFcRnFc gamma receptorFc epsilon receptorFc alpha receptor

Fc receptor-targeted therapies function through several distinct mechanisms: inhibition of the neonatal Fc receptor (FcRn) to accelerate the clearance of pathogenic IgG autoantibodies; enhancement of antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis (ADCP) by optimizing binding to activating Fc gamma receptors (FcγRs); blocking of the high-affinity IgE receptor (FcεRI) pathway to prevent mast cell degranulation in allergic diseases; and the use of soluble decoy receptors or engagement of inhibitory receptors like FcγRIIB to suppress overactive immune responses.