Adenosine signaling and the immune system: When a lot could be too much

Adenosine is increasingly recognized as a key mediator of the immune response. Signals delivered by extracellular adenosine are detected and transduced by G-protein-coupled cell-surface receptors, classified into four subtypes: A₁, A_2A, A_2B and A₃. These receptors, expressed virtually on all immune cells, modulate all aspects of immune/inflammatory responses. These immunoregulatory effects, which are mostly anti-inflammatory, contribute to the general tissue protective effects of adenosine and its receptors. In some instances, however, the effect of adenosine on the immune system is deleterious, as prolonged adenosine signaling can hinder anti-tumor and antibacterial immunity, thereby promoting cancer development and progression and sepsis, respectively.