Dendritic cells tolerized with adenosine A2AR agonist attenuate acute kidney injury
Li Li, … , Diane L. Rosin, Mark D. Okusa
Li Li, … , Diane L. Rosin, Mark D. Okusa
Published October 24, 2012
Citation Information: J Clin Invest. 2012;122(11):3931-3942. https://doi.org/10.1172/JCI63170.
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Dendritic cells tolerized with adenosine A2AR agonist attenuate acute kidney injury

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.

Authors

Li Li, Liping Huang, Hong Ye, Steven P. Song, Amandeep Bajwa, Sang Ju Lee, Emily K. Moser, Katarzyna Jaworska, Gilbert R. Kinsey, Yuan J. Day, Joel Linden, Peter I. Lobo, Diane L. Rosin, Mark D. Okusa

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Figure 3

DCs-αGC-ATL313 administered before or after ischemia protect kidneys from moderate IRI.

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DCs-αGC-ATL313 administered before or after ischemia protect kidneys fro...
(A) The experimental process was similar to that in Figure 2, except that WT mice were subjected to 28 minutes of moderate ischemia and 24 of hours reperfusion. Plasma creatinine was measured 24 hours after sham operation or IRI. n = 2–4. (B) The experiment was similar to that in A, except that mice were subjected to renal artery clamping (instead of renal pedicle clamping) for 35 minutes; plasma creatinine was measured after 24 hours of reperfusion. n = 4 and 5 for DCs-αGC and DCs-αGC-ATL313, respectively. (C) DCs-αGC-ATL313 were administered 1 or 6 hours after moderate (28 minutes) kidney ischemia, and plasma creatinine was measured after 24 or 48 hours of reperfusion (from the end of the ischemic period). n = 3–5. *P < 0.05; **P < 0.01; ***P < 0.001. Values are mean ± SEM.