title: 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.affiliation: Department of Medicine, University of Virginia, Charlottesville, Virginia, USA. ll3m@virginia.edu
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Liping
authors.initials: L
authors.lastname: Huang
authors.forename: Hong
authors.initials: H
authors.lastname: Ye
authors.forename: Steven P
authors.initials: SP
authors.lastname: Song
authors.forename: Amandeep
authors.initials: A
authors.lastname: Bajwa
authors.forename: Sang Ju
authors.initials: SJ
authors.lastname: Lee
authors.forename: Emily K
authors.initials: EK
authors.lastname: Moser
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Jaworska
authors.forename: Gilbert R
authors.initials: GR
authors.lastname: Kinsey
authors.forename: Yuan J
authors.initials: YJ
authors.lastname: Day
authors.forename: Joel
authors.initials: J
authors.lastname: Linden
authors.forename: Peter I
authors.initials: PI
authors.lastname: Lobo
authors.forename: Diane L
authors.initials: DL
authors.lastname: Rosin
authors.forename: Mark D
authors.initials: MD
authors.lastname: Okusa
mesh_terms: D058186:Acute Kidney Injury / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D058908:Adenosine A2 Receptor Agonists / Q000494:pharmacology*; D000818:Animals; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology / Q000637:transplantation; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects* / Q000235:genetics; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D007668:Kidney / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000276:immunology / Q000473:pathology; D043705:Receptor, Adenosine A2A / Q000235:genetics / Q000276:immunology*; D015427:Reperfusion Injury / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000517:prevention & control
chemical_list: D058908:Adenosine A2 Receptor Agonists; D043705:Receptor, Adenosine A2A; D007371:Interferon-gamma