Regulation of NK cell-mediated tubular epithelial cell death and kidney ischemia-reperfusion injury by the NKR-P1B receptor and Clr-b

Abstract

Renal ischemia-reperfusion injury (IRI) occurs following reduced renal blood flow and is a major cause of acute injury in both native and transplanted kidneys. We have previously demonstrated that NK cells can mediate tubular cell death and kidney IRI. Natural killer receptor-protein 1B (NKR-P1B) has been shown to interact with C-type lectin-related protein B (Clr-b), resulting in the suppression of NK cell-mediated cytotoxicity. Clr-b mRNA and protein expression in the kidney were up-regulated after renal IRI. Similar upregulation of Clr-b expression was seen in cytokine-challenged primary-cultured tubular epithelial cells (TEC). Furthermore, NK cytotoxicity assays demonstrated enhanced necrotic death in TEC after Clr-b siRNA knockdown. Our results indicate that Clr-b expression in TEC and the kidney is upregulated after injury. The blockade of Clr-b enhances NK cell-mediated TEC death and kidney injury. These studies suggest that enhancing the inhibitory Clr-b in transplant patients may protect the kidney from NK cell-mediated cytotoxicity