Progress on role of extracellular ATP and its metabolite adenosine in immunoregulation: Review

Extracellular adenosine triphosphate (ATP), as an extracellular messenger, participates in the immune response and inflammatory process, and is considered as a dangerous signal molecule. On one hand, extracellular ATP promotes inflammation through activating ATP receptor represented by P2X7 (P2 purinergic receptor) and downstream NLRP3 inflammasome assembly. On the other hand, it plays an anti-inflammatory role through conversion to adenosine by CD39 and CD73 on the cell surface and acting via adenosine receptor (P1 purinergic receptor). Both P1 and P2 purinergic receptors are distributed in most cells, and vary in their affinity to ATP and adenosine. Injury, stress and inflammation can induce the release of nucleotides. Recent studies have shown that as endogenous tissue-derived signal molecules, extracellular ATP and its metabolite adenosine play a vital role in immunoregulation through purinergic metabolic pathway. The change of ATP and adenosine concentration in tissue microenvironment can affect the occurrence and resolution of inflammation, which has guiding significance for exploring the prevention and treatment strategies of inflammatory diseases. In this review, we summarize that CD39/CD73 synergistically regulates the balance of extracellular ATP and adenosine, thus influencing immune cell functions through P2 receptor and P1 receptor signaling pathway.