title: NK cells induce apoptosis in tubular epithelial cells and contribute to renal ischemia-reperfusion injury.
abstract: Renal ischemia-reperfusion injury (IRI) can result in acute renal failure with mortality rates of 50% in severe cases. NK cells are important participants in early-stage innate immune responses. However, their role in renal tubular epithelial cell (TEC) injury in IRI is currently unknown. Our data indicate that NK cells can kill syngeneic TEC in vitro. Apoptotic death of TEC in vitro is associated with TEC expression of the NK cell ligand Rae-1, as well as NKG2D on NK cells. In vivo following IRI, there was increased expression of Rae-1 on TEC. FACS analyses of kidney cell preparations indicated a quantitative increase in NKG2D-bearing NK cells within the kidney following IRI. NK cell depletion in wild-type C57BL/6 mice was protective, while adoptive transfer of NK cells worsened injury in NK, T, and B cell-null Rag2(-/-)gamma(c)(-/-) mice with IRI. NK cell-mediated kidney injury was perforin (PFN)-dependent as PFN(-/-) NK cells had minimal capacity to kill TEC in vitro compared with NK cells from wild-type, FasL-deficient (gld), or IFN-gamma(-/-) mice. Taken together, these results demonstrate for the first time that NK cells can directly kill TEC and that NK cells contribute substantially to kidney IRI. NK cell killing may represent an important underrecognized mechanism of kidney injury in diverse forms of inflammation, including transplantation.
authors.affiliation: The Multi-Organ Transplant Program, London Health Sciences Centre, London, Ontario, Canada. zhuxu.zhang@lhsc.on.ca
authors.forename: Zhu-Xu
authors.initials: ZX
authors.lastname: Zhang
authors.forename: Shuang
authors.initials: S
authors.lastname: Wang
authors.forename: Xuyan
authors.initials: X
authors.lastname: Huang
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Min
authors.forename: Hongtao
authors.initials: H
authors.lastname: Sun
authors.forename: Weihua
authors.initials: W
authors.lastname: Liu
authors.forename: Bertha
authors.initials: B
authors.lastname: Garcia
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Jevnikar
mesh_terms: D019264:Adoptive Transfer / Q000379:methods; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D004847:Epithelial Cells / Q000276:immunology* / Q000473:pathology; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000473:pathology; D007674:Kidney Diseases / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D016030:Kidney Transplantation / Q000276:immunology; D007684:Kidney Tubules / Q000276:immunology* / Q000473:pathology; D007694:Killer Cells, Natural / Q000276:immunology* / Q000473:pathology / Q000637:transplantation; D051379:Mice; D018345:Mice, Knockout; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000235:genetics / Q000276:immunology; D034521:Nuclear Matrix-Associated Proteins / Q000235:genetics / Q000276:immunology; D029543:Nucleocytoplasmic Transport Proteins / Q000235:genetics / Q000276:immunology; D052899:Pore Forming Cytotoxic Proteins / Q000235:genetics / Q000276:immunology; D015427:Reperfusion Injury / Q000235:genetics / Q000276:immunology* / Q000473:pathology
chemical_list: C527086:Klrk1 protein, mouse; D055655:NK Cell Lectin-Like Receptor Subfamily K; D034521:Nuclear Matrix-Associated Proteins; D029543:Nucleocytoplasmic Transport Proteins; D052899:Pore Forming Cytotoxic Proteins; C490521:Rae1 protein, mouse; C483886:perforin, mouse