Complement 3a Receptor (C3aR)

C3aR, also known as C3a receptor, is a single polypeptide chain that spans the membrane seven times, belonging to the family of G-protein-coupled receptors (GPCRs). The receptor contains a large second extracellular loop of approximately 175 amino acids compared to about 30 amino acids for most GPCRs including the C5a receptor and FPR family. This loop has been revealed to play a role in C3a binding and receptor activation.

C3aR is primarily found on myeloid and lymphoid cells. It serves as a key chemotactic mediator in the immune system. C3aR interacts with C3a polypeptides (the best known as chemotactic and inflammatory cytokines) to facilitate the movement of neutrophils, monocytes, and macrophages to the site of inflammation, where they promote the phagocytosis of opsonized foreign molecules and altered self molecules. C3aR also acts as an immune checkpoint receptor. Complement signaling through C3aR expressed on effector T lymphocytes inhibits the production of the cytokine interleukin-10 (IL-10). In various inflammatory-related diseases, C3aR signaling exhibits a protective role. For example, C3aR signaling has been revealed to act as a potent regulator of ethanol-induced adipose inflammation in a murine model with alcohol-related liver disease (ALD). C3aR signaling has been also shown a protective role in the development of atherosclerosis through negative regulation of proinflammatory responses regulated by the C3a-C3aR axis and regulating the macrophage toward the anti-inflammatory phenotype.

Fig.1 Proposed interaction between FcεRI and C3aR leading to mast cell activation. (Ali, 2005)

Reference

1. Ali, H.; et al. Anaphylatoxin C3a receptors in asthma. Respiratory Research. 2005, 6: 19.