The role of the CD39–CD73–adenosine pathway in liver disease

Abstract Extracellular adenosine triphosphate (ATP) is a danger signal released by dying and damaged cells, and it functions as an immunostimulatory signal that promotes inflammation. The ectonucleotidases CD39/ectonucleoside triphosphate diphosphohydrolase‐1 and CD73/ecto‐5′‐nucleotidase are cell‐surface enzymes that breakdown extracellular ATP into adenosine. This drives a shift from an ATP‐driven proinflammatory environment to an anti‐inflammatory milieu induced by adenosine. The CD39–CD73–adenosine pathway changes dynamically with the pathophysiological context in which it is embedded. Accumulating evidence suggests that CD39 and CD73 play important roles in liver disease as critical components of the extracellular adenosinergic pathway. Recent studies have shown that the modification of the CD39–CD73–adenosine pathway alters the liver's response to injury. Moreover, adenosine exerts different effects on the pathophysiology of the liver through different receptors. In this review, we aim to describe the role of the CD39–CD73–adenosine pathway and adenosine receptors in liver disease, highlighting potential therapeutic targets in this pathway, which will facilitate the development of therapeutic strategies for the treatment of liver disease.