Fc gamma receptor and transporter (FcRn) (FcRn)

The Fc gamma receptor and transporter (FcRn) is a cell surface receptor that binds the Fc region of monomeric immunoglobulin G (IgG), playing a critical role in transferring passive humoral immunity from mother to fetus or neonate across the placenta or intestinal epithelium. In adults, FcRn resides primarily in endosomal compartments, where it exhibits pH-dependent binding: high affinity for IgG at acidic pH (<6.5) enables sorting and recycling of internalized IgG and serum albumin to the cell surface at neutral pH, thereby extending their half-lives and preventing lysosomal degradation. FcRn also facilitates the transcytosis of IgG across epithelial barriers, such as in the intestine, and co-expression with Fc gamma receptors in antigen-presenting cells like macrophages and dendritic cells enhances antigen uptake, intracellular trafficking of IgG-immune complexes, and MHC class II-mediated presentation. Its expression is upregulated by proinflammatory cytokine TNF-α and downregulated by anti-inflammatory IFN-γ, linking it to immune regulation. In disease contexts, FcRn at the blood-brain barrier regulates IgG movement into and out of the central nervous system, with implications for neurological disorders and immune surveillance; hepatic FcRn directs albumin recirculation, influencing hepatocyte toxicity sensitivity. Therapeutically, FcRn represents a target for modulating IgG levels in autoimmune and inflammatory conditions, though challenges include balancing immunity without compromising protein homeostasis.

Other names

neonatal Fc receptorneonatal fragment crystallizable receptor

pH-dependent binding to IgG Fc region in acidic endosomes for recycling to cell surface, avoiding lysosomal degradation; transport of IgG-immune complexes for antigen presentation