Adhesion GPCRs in Regulating Immune Responses and Inflammation

The adhesion family comprises one of the five major clades of G protein-coupled receptors (GPCRs). Unlike conventional GPCRs, adhesion GPCRs (aGPCRs) have extended ectodomains with various protein folds that facilitate protein-protein interactions and, hence, putative cellular adhesive functions. Juxtaposed to the seven-pass transmembrane domain is a GPCR autoproteolysis-inducing domain that enables autoproteolytic cleavage of the receptor, resulting in a bipartite structure of many aGPCRs. aGPCRs are widely distributed and play critical roles in many developmental processes; yet, the underlying mechanisms of activation and signal transduction have emerged only recently. About one-third of the 33 human aGPCRs are expressed in hematopoietic stem, progenitor, or mature cells, where they define distinct cellular populations. Recent studies have demonstrated roles of aGPCR in the control of innate effector functions and the susceptibility for and onset of (auto) inflammatory conditions. We here discuss the current knowledge about aGPCRs in the regulation of immune responses and inflammation.