CD39 and CD73 in immunity and inflammation

• CD39 and CD73 are important for calibrating the duration, magnitude, and composition of the ‘purinergic halo’ surrounding immune cells.
• CD39 and CD73 degrade ATP, ADP, and AMP to adenosine; they can be viewed as ‘immunological switches’ that shift ATP-driven proinflammatory immune cell activity toward an anti-inflammatory state mediated by adenosine.
• CD39 and CD73 are highly expressed on the surface of Foxp3+ Tregs and have been increasingly used as markers of Tregs.
• CD39 and CD73 are important for the immunosuppressive activity of Tregs.
• CD39 and CD73 generate an immunosuppressed environment, characterized by increased adenosine levels, which promotes the development and progression of cancer.

The enzymatic activities of CD39 and CD73 play strategic roles in calibrating the duration, magnitude, and chemical nature of purinergic signals delivered to immune cells through the conversion of ADP/ATP to AMP and AMP to adenosine, respectively. This drives a shift from an ATP-driven proinflammatory environment to an anti-inflammatory milieu induced by adenosine. The CD39/CD73 pathway changes dynamically with the pathophysiological context in which it is embedded. It is becoming increasingly appreciated that altering this catabolic machinery can change the course or dictate the outcome of several pathophysiological events, such as AIDS, autoimmune diseases, infections, atherosclerosis, ischemia–reperfusion injury, and cancer, suggesting these ectoenzymes are novel therapeutic targets for managing a variety of disorders.