The role of P2Y receptors in regulating immunity and metabolism.

P2Y receptors are G protein-coupled receptors whose physiological agonists are the nucleotides ATP, ADP, UTP, UDP and UDP-glucose. Eight P2Y receptors have been cloned in humans: P2Y1R, P2Y2R, P2Y4R, P2Y6R, P2Y11R, P2Y12R, P2Y13R and P2Y14R. P2Y receptors are expressed in lymphoid tissues such as thymus, spleen and bone marrow where they are expressed on lymphocytes, macrophages, dendritic cells, neutrophils, eosinophils, mast cells, and platelets. P2Y receptors regulate many aspects of immune cell function, including phagocytosis and killing of pathogens, antigen presentation, chemotaxis, degranulation, cytokine production, and lymphocyte activation. Consequently, P2Y receptors shape the course of a wide range of infectious, autoimmune, and inflammatory diseases. P2Y12R ligands have already found their way into the therapeutic arena, and we envision additional ligands as future drugs for the treatment of diseases caused by or associated with immune dysregulation.