Sulfatide-Reactive Natural Killer T Cells Abrogate Ischemia-Reperfusion Injury
- 1 July 2011
- journal article
- Published by Ovid Technologies (Wolters Kluwer Health) in Journal of the American Society of Nephrology
- Vol. 22 (7), 1305-1314
- https://doi.org/10.1681/asn.2010080815
Abstract
There is a significant immune response to ischemia-reperfusion injury (IRI), but the role of immunomodulatory natural killer T (NKT) cell subtypes is not well understood. Here, we compared the severity of IRI in mice deficient in type I/II NKT cells (CD1d−/−) or type I NKT cells (Jα18−/−). The absence of NKT cells, especially type II NKT cells, accentuated the severity of renal injury, whereas repletion of NKT cells attenuated injury. Adoptively transferred NKT cells trafficked into the tubulointerstitium, which is the primary area of injury. Sulfatide-induced activation of type II NKT cells protected kidneys from IRI, but inhibition of NKT cell recruitment enhanced injury. In co-culture experiments, sulfatide-induced activation of NKT cells from either mice or humans attenuated apoptosis of renal tubular cells after transient hypoxia via hypoxia-inducible factor (HIF)-1α and IL-10 pathways. Renal tissue of patients with acute tubular necrosis (ATN) frequently contained NKT cells, and the number of these cells tended to negatively correlate with ATN severity. In summary, sulfatide-reactive type II NKT cells are renoprotective in IRI, suggesting that pharmacologic modulation of NKT cells may protect against ischemic injury.Keywords
This publication has 43 references indexed in Scilit:
- Regulatory T cells contribute to the protective effect of ischemic preconditioning in the kidneyKidney International, 2010
- Regulatory T Cells Suppress Innate Immunity in Kidney Ischemia-Reperfusion InjuryJournal of the American Society of Nephrology, 2009
- Xenon Preconditioning Protects against Renal Ischemic-Reperfusion Injury via HIF-1α ActivationJournal of the American Society of Nephrology, 2009
- Acute Kidney Injury Increases Risk of ESRD among ElderlyJournal of the American Society of Nephrology, 2009
- Cross‐regulation between distinct natural killer T cell subsets influences immune response to self and foreign antigensJournal of Cellular Physiology, 2008
- Hypoxia controls CD4+CD25+ regulatory T‐cell homeostasis via hypoxia‐inducible factor‐1αEuropean Journal of Immunology, 2008
- NKT Cells Inhibit the Development of Experimental Crescentic GlomerulonephritisJournal of the American Society of Nephrology, 2008
- Hypoxia stimulus: An adaptive immune response during dendritic cell maturationKidney International, 2008
- Type II NKT cell–mediated anergy induction in type I NKT cells prevents inflammatory liver diseaseJCI Insight, 2007
- THE CD1 SYSTEM: Antigen-Presenting Molecules for T Cell Recognition of Lipids and GlycolipidsAnnual Review of Immunology, 1999