The Importance of C5aR2 in Neutrophil Function and Its Impact on Neutrophil-mediated Diseases

Abstract

The two receptors for the anaphylatoxin C5a are critically involved in the recruitment of immune cells and activate these cells at sites of inflammation. The pro-inflammatory function of C5aR1 in these processes is well established, whereas the functional properties of the second C5a receptor, C5aR2, in inflammation remain enigmatic. We recently reported a pro-inflammatory contribution of C5aR2 to the pathogenesis of the prototypical autoimmune skin blistering disease epidermolysis bullosa acquisita (EBA). Deficiency of C5aR2 ameliorated the disease phenotype in an antibody transfer model of EBA and reduced neutrophil migration and activation in vitro. Here, we discuss not only these data, but the crosstalk of C5aR2 with Fcγ receptors, and the effect of C5a desArg stimulation on neutrophils. In addition, we highlight the cellular location of C5aR2, its functional dependence on concomitant C5aR1 expression, and its importance for therapeutic strategies targeting the C5a receptor pathways in neutrophil-mediated diseases.