Adenosinergic metabolism pathway: an emerging target for improving outcomes of solid organ transplantation

Extracellular nucleotides are widely recognized as crucial modulators of immune responses in peripheral tissues. Adenosine triphosphate (ATP) and adenosine are key components of extracellular nucleotides, the balance of which contributes to immune homeostasis. Under tissue injury, ATP exerts its pro-inflammatory function, while the adenosinergic pathway rapidly degrades ATP to immunosuppressive adenosine, thus inhibiting excessive and uncontrolled inflammatory responses. Previous reviews have explored the immunoregulatory role of extracellular adenosine in various pathological conditions, especially inflammation and malignancy. However, current knowledge regarding adenosine and adenosinergic metabolism in the context of solid organ transplantation remains fragmented. In this review, we summarize the latest information on adenosine metabolism and the mechanisms by which it suppresses the effector function of immune cells, as well as highlight the protective role of adenosine in all stages of solid organ transplantation, including reducing ischemia reperfusion injury during organ procurement, alleviating rejection, and promoting graft regeneration after transplantation. Finally, we discuss the potential for future clinical translation of adenosinergic pathway in solid organ transplantation.