C3aR

C3a receptor (C3aR) is a G protein-coupled receptor that binds the anaphylatoxin C3a, a product of complement component C3 activation. In humans, the receptor is encoded by the C3AR1 gene and is expressed on a range of cell types, including neutrophils, eosinophils, mast cells, basophils, monocytes, macrophages, dendritic cells, and various endothelial and epithelial cells.

Upon C3a binding, C3aR couples to intracellular G proteins and triggers signaling pathways that raise intracellular calcium, activate mitogen-activated protein kinases, and promote chemotaxis, degranulation, and the release of inflammatory mediators such as histamine and cytokines. These responses contribute to acute inflammation and the recruitment and activation of immune cells. The receptor can also influence adaptive immune responses and antigen presentation in some contexts.

C3aR can be activated by the C3a peptide and, at lower affinity, by the des-Arg form of C3a. The pharmacology of C3aR varies between species, and receptor desensitization and cross-talk with other receptors can shape the signaling outcomes arising from C3a stimulation.

In disease contexts, C3aR has been implicated in a range of inflammatory and allergic conditions, including asthma, sepsis, rheumatoid arthritis, and neuroinflammatory disorders. Studies in animal models show that loss or blockade of C3aR can attenuate certain inflammatory phenotypes, while in other settings C3aR activity may aid host defense or tissue repair.

Therapeutically, C3aR has been explored as a target for anti-inflammatory interventions, with research focusing on peptide-based and other antagonists. The receptor’s role in immune regulation and its interactions within the complement system continue to be active areas of investigation.