Sulfatide-Reactive Natural Killer T Cells Abrogate Ischemia-Reperfusion Injury

• DOI: 10.1681/asn.2010080815
• Publication Date: 2011-05-27T02:33:09Z
• Authors: Seung Hee Yang; Jung Pyo Lee; Hye Ryoun Jang; Ran-hui Cha; Seung Seok Han; Un Sil Jeon; Dong Ki Kim; Junghan Song; Dong-Sup Lee; Yon Su Kim
• Keywords: Male; 0301 basic medicine; Sulfoglycosphingolipids; Epithelial Cells; Acute Kidney Injury; Lymphocyte Activation; Interleukin-10; 3. Good health; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Kidney Tubules; Reperfusion Injury; Animals; Cytokines; Natural Killer T-Cells; Hypoxia-Inducible Factor 1; Hypoxia

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.