Complement C3a receptor 1 and Complement C5a receptor 1 (C3aR and C5aR1)

The Complement C3a receptor (C3aR) and Complement C5a receptor 1 (C5aR1) are G protein-coupled receptors that mediate the biological effects of the anaphylatoxins C3a and C5a, which are potent cleavage products of the complement system (UniProt P46089, P21730). These receptors are expressed on various cell types, including mesenchymal stem cells (MSCs), where they play a pivotal role in regulating cellular migration and homing to sites of inflammation (PubMed: 16443817). Activation of C3aR and C5aR on MSCs triggers intracellular signaling pathways such as PI3K/Akt and MAPK/ERK, which are essential for the mobilization of these cells during tissue injury and repair (PubMed: 24166361). In addition to chemotaxis, these receptors modulate the immunomodulatory and differentiation potential of MSCs, influencing the local inflammatory microenvironment and stem cell niche. Dysregulation of the C3a/C5a-receptor axes is associated with numerous inflammatory and autoimmune conditions, such as ANCA-associated vasculitis and rheumatoid arthritis. Consequently, these receptors are significant therapeutic targets; for instance, Avacopan is an FDA-approved C5aR1 antagonist used to reduce vascular inflammation. Targeting these receptors on MSCs specifically offers a potential avenue for enhancing the efficacy of cell-based therapies or controlling endogenous stem cell responses in regenerative medicine.

Other names

C3AR1C5AR1CD88C3a receptorC5a receptorComplement component 3a receptor 1Complement component 5a receptor 1C5aR

Antagonism of C3a and C5a receptors to block downstream signaling pathways such as MAPK/ERK and PI3K/Akt, thereby inhibiting the chemotactic recruitment of inflammatory cells and modulating the activation and migration of mesenchymal stem cells.