Complement C3a receptor (C3aR)

Complement C3a receptor (C3aR) is a class A G protein-coupled receptor predominantly expressed on cells of the immune system, including granulocytes, macrophages, and T lymphocytes[1][6]. It mediates the actions of the anaphylatoxin C3a, a cleavage product of complement component C3, by triggering intracellular signaling that leads to chemotaxis, cytokine release, inflammatory cell activation, and modulation of immune responses[1][4][5]. C3aR signals through canonical GPCR pathways involving G proteins, leading to diverse functional effects such as mast cell degranulation, T cell activation, angiogenesis, and both pro- and anti-inflammatory effects depending on the context[1][3][4]. Its dual immunomodulatory roles mean it can contribute to pathological conditions (inflammation, fibrosis, certain cancers), but also confer protective activities during infection or tissue repair[4][6]. Antagonists and agonists of C3aR are under investigation for the treatment of inflammatory, autoimmune, renal, allergic, and cancer-related diseases, but specificity and safety require careful consideration due to its broad, context-dependent biology[2][4][5][6]. Crystal and cryo-EM structures, including those with the small-molecule agonist JR14a, have clarified its activation mechanism and may facilitate rational drug design[3][5][7].

Other names

Complement component 3a receptorC3a anaphylatoxin receptorC3aR1

Agonists activate C3aR to initiate G protein-mediated signal transduction, driving chemotaxis, cytokine production, and cell activation[3][5]. Antagonists inhibit C3aR function, blocking pro-inflammatory signal transduction and reducing immune cell infiltration and tissue inflammation[2][4][6].