Novel insights into the expression pattern of anaphylatoxin receptors in mice and men

The anaphylatoxins (AT) C3a and C5a play important roles as mediators of inflammation. Further, they regulate and control multiple innate and adaptive immune responses through binding and activation of their cognate G protein-coupled receptors, i.e. C3a receptor (C3aR), C5a receptor 1 (C5aR1) and C5a receptor 2 (C5aR2), although the latter lacks important sequence motifs for G protein-coupling. Based on their pleiotropic functions, they contribute not only to tissue homeostasis but drive, perpetuate and resolve immune responses in many inflammatory diseases including infections, malignancies, autoimmune as well as allergic diseases. During the past few years, transcriptome expression data provided detailed insights into AT receptor tissue mRNA expression. In contrast, our understanding of cellular AT receptor expression in human and mouse tissues under steady and inflammatory conditions is still sketchy. Ligand binding studies, flow cytometric and immunohistochemical analyses convincingly demonstrated tissue-specific C5aR1 expression in various cells of myeloid origin. However, a detailed map for C3aR or C5aR2 expression in human or mouse tissue cells is still lacking. Also, reports about AT expression in lymphoid cells is still controversial. To understand the multiple roles of the ATs in the innate and adaptive immune networks, a detailed understanding of their receptor expression in health and disease is required. Recent findings obtained with novel GFP or tdTomato AT-receptor knock-in mice provide detailed insights into their expression pattern in tissue immune and stroma cells. Here, we will provide an update about our current knowledge of AT receptor expression pattern in humans and mice.