The Role of Purinergic Signalling in Inflammatory Disorders

Abstract The purinergic signalling system comprises extracellular nucleotides such as adenosine triphosphate (ATP), which signals through the two P2 receptor subfamilies; P2X (P2X1-7) and P2Y (P2Y1, 2, 4, 6, 11, 12, 13, and 14). Breakdown of ATP to adenosine diphosphate (ADP) and adenosine monophosphate (AMP), by the ecto-nucleotidase ecto-nucleoside triphosphate diphosphohydrolase-1 (CD39), and finally AMP to adenosine, by ecto-5’-nucleotidase (CD73) allows activation of adenosine receptors (A1, A2A, A2B and A3). Purinergic signalling is important in inflammation and immunity, and has been implicated in transplantation, including hematopoietic stem cell transplantation (HSCT) and a major complication of allogeneic HSCT; graft-versus-host disease (GVHD). In allogeneic mouse models of GVHD, activation of P2X7, or blockade of CD73 or A2A, worsen disease, while A2A activation reduces GVHD.