Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Pathology

Supervisor

Zhu-Xu Zhang

2nd Supervisor

Anthony M. Jevnikar

Joint Supervisor

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.

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