Dendritic cells tolerized with adenosine A2AR agonist attenuate acute kidney injury.
J Clin Invest
; 122(11): 3931-42, 2012 Nov.
Article
en En
| MEDLINE
| ID: mdl-23093781
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Células Dendríticas
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Receptor de Adenosina A2A
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Lesión Renal Aguda
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Agonistas del Receptor de Adenosina A2
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Tolerancia Inmunológica
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Riñón
Límite:
Animals
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Humans
Idioma:
En
Revista:
J Clin Invest
Año:
2012
Tipo del documento:
Article
País de afiliación:
Estados Unidos