Purinergic signaling in the immune system

Extracellular ATP and its metabolite adenosine are increasingly recognized as key mediators of the immune response. Depending on the concentration, ATP may act as an immunostimulant or an immunodepressant, while adenosine is generally acknowledged to be a potent immunosupressor molecule. Signals delivered by extracellular ATP and adenosine are detected and transduced by P2 and P1 receptors, respectively. Virtually all immune cells express P2 and P1 receptors, thus purinergic signaling affects all aspects of immunity and inflammation. This realization has prompted a burst of novel investigations aimed at the design and synthesis of P2- or P1-targeted drugs for the treatment of chronic inflammatory diseases and cancer. In this review we will summarize the most recent developments in this field.