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J Clin Invest. 2012 Nov;122(11):3931-42. doi: 10.1172/JCI63170. Epub 2012 Oct 24.

Dendritic cells tolerized with adenosine A₂AR agonist attenuate acute kidney injury.

Author information

1
Department of Medicine, University of Virginia, Charlottesville, Virginia, USA. ll3m@virginia.edu

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 (A₂AR) agonists protect kidneys from IRI through their actions on leukocytes. In this study, we showed that mice with A₂AR-deficient DCs are more susceptible to kidney IRI and are not protected from injury by A₂AR agonists. In addition, administration of DCs treated ex vivo with an A₂AR 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. A₂AR agonists had no effect on DC antigen presentation or on Tregs. We conclude that ex vivo A₂AR-induced tolerized DCs suppress NKT cell activation in vivo and provide a unique and potent cell-based strategy to attenuate organ IRI.

PMID:
23093781
PMCID:
PMC3484444
DOI:
10.1172/JCI63170
[Indexed for MEDLINE]
Free PMC Article

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