Activation of adenosine A2A receptors (A2AR) reduces inflammation by generally inhibiting the activation of
pro-inflammatory cells, decreasing endothelial adhesion molecule expression and reducing the release of proinflammatory
cytokine mediators. Numerous preclinical studies using selective A2AR agonists, antagonists, A2AR knockout as well as
chimeric mice have suggested the therapeutic potential of A2AR agonists for the treatment of ischemia reperfusion injury
(IRI) and autoimmune diseases. This review summarizes the immunosuppressive actions of A2AR agonists in murine IRI
models of liver, kidney, heart, lung and CNS, and gives details on the cellular effects of A2AR activation in neutrophils,
macrophages, dendritic cells, natural killer cells, NKT cells, T effector cells and CD4+CD25+FoxP3+ T regulatory cells.
This is discussed in the context of cytokine mediators involved in inflammatory cascades. Whilst the role of adenosine receptor
agonists in various models of autoimmune disease has been well-documented, very little information is available
regarding the role of A2AR activation in type 1 diabetes mellitus (T1DM). An overview of the pathogenesis of T1DM as
well as early islet graft rejection in the immediate peri-transplantation period offers insight regarding the use of A2AR
agonists as a beneficial intervention in clinical islet transplantation, promoting islet graft survival, minimizing early islet
loss and reducing the number of islets required for successful transplantation, thereby increasing the availability of this
procedure to a greater number of recipients. In summary, the use of A2AR agonists as a clinical intervention in IRI and as
an adjunct to clinical immunesuppressive regimen in islet transplantation is highlighted.