Dendritic cells tolerized with adenosine A2AR agonist attenuate acute kidney injury

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

Research output: Contribution to journalArticle

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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 anti-inflammatory 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.

Original languageEnglish (US)
Pages (from-to)3931-3942
Number of pages12
JournalJournal of Clinical Investigation
Volume122
Issue number11
DOIs
StatePublished - Nov 1 2012

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Purinergic P1 Receptor Agonists
Reperfusion Injury
Acute Kidney Injury
Adenosine
Dendritic Cells
Natural Killer T-Cells
Kidney
Purinergic P1 Receptors
Antigen Presentation
Leukocytes
Anti-Inflammatory Agents
Inflammation
Wounds and Injuries

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Dendritic cells tolerized with adenosine A2AR agonist attenuate acute kidney injury. / Li, Li; Huang, Liping; Ye, Hong; Song, Steven P.; Bajwa, Amandeep; Lee, Sang Ju; Moser, Emily K.; Jaworska, Katarzyna; Kinsey, Gilbert R.; Day, Yuan J.; Linden, Joel; Lobo, Peter I.; Rosin, Diane L.; Okusa, Mark D.

In: Journal of Clinical Investigation, Vol. 122, No. 11, 01.11.2012, p. 3931-3942.

Research output: Contribution to journalArticle

Li, L, Huang, L, Ye, H, Song, SP, Bajwa, A, Lee, SJ, Moser, EK, Jaworska, K, Kinsey, GR, Day, YJ, Linden, J, Lobo, PI, Rosin, DL & Okusa, MD 2012, 'Dendritic cells tolerized with adenosine A2AR agonist attenuate acute kidney injury', Journal of Clinical Investigation, vol. 122, no. 11, pp. 3931-3942. https://doi.org/10.1172/JCI63170
Li, Li ; Huang, Liping ; Ye, Hong ; Song, Steven P. ; Bajwa, Amandeep ; Lee, Sang Ju ; Moser, Emily K. ; Jaworska, Katarzyna ; Kinsey, Gilbert R. ; Day, Yuan J. ; Linden, Joel ; Lobo, Peter I. ; Rosin, Diane L. ; Okusa, Mark D. / Dendritic cells tolerized with adenosine A2AR agonist attenuate acute kidney injury. In: Journal of Clinical Investigation. 2012 ; Vol. 122, No. 11. pp. 3931-3942.
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