Abstract
DC-mediated NKT cell activation is critical in initiating the immune response following kidney ischemia/reperfusion injury (IRI), which mimics human acute kidney injury (AKI). Adenosine is an important antiinflammatory molecule in tissue inflammation, and adenosine 2A receptor (A&sub2;AR) agonists protect kidneys from IRI through their actions on leukocytes. In this study, we showed that mice with A&sub2;AR-deficient DCs are more susceptible to kidney IRI and are not protected from injury by A&sub2;AR agonists. In addition, administration of DCs treated ex vivo with an A&sub2;AR agonist protected the kidneys of WT mice from IRI by suppressing NKT production of IFN-γ and by regulating DC costimulatory molecules that are important for NKT cell activation. A&sub2;AR agonists had no effect on DC antigen presentation or on Tregs. We conclude that ex vivo A&sub2;AR-induced tolerized DCs suppress NKT cell activation in vivo and provide a unique and potent cell-based strategy to attenuate organ IRI.