NKT cells are important mediators of hepatic ischemia-reperfusion injury
| Autor: | James A, Richards, Stephen J, Wigmore, Stephen M, Anderton, Sarah E M, Howie |
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| Rok vydání: | 2017 |
| Předmět: |
Male
Ischemia-reperfusion injury (IRI) IRI ischemia-reperfusion injury CD3 Complex T-Lymphocytes NKT natural killer T cell T cells Mice Transgenic SEM standard error of the mean TNF tumour necrosis factor Lymphocyte Depletion Article Mice Acute liver injury Animals Humans MHC major histocompatibility complex IFN interferon Liver surgery DCD donation after cardiac death Homeodomain Proteins Mice Knockout Transplantation TCR T cell receptor Liver Transplantation IL interleukin Mice Inbred C57BL IgM immunoglobulin M NKT cells Liver Th T helper cell Reperfusion Injury Natural Killer T-Cells TReg regulatory T Cells (CD3 + CD4 + FoxP3 +) Natural killer cells NK natural killer DAMPs Danger Associated Molecular Patterns |
| Zdroj: | Transplant Immunology |
| ISSN: | 1878-5492 |
| Popis: | Introduction IRI results from the interruption then reinstatement of an organ's blood supply, and this poses a significant problem in liver transplantation and resectional surgery. In this paper, we explore the role T cells play in the pathogenesis of this injury. Materials & methods We used an in vivo murine model of warm partial hepatic IRI, genetically-modified mice, in vivo antibody depletion, adoptive cell transfer and flow cytometry to determine which lymphocyte subsets contribute to pathology. Injury was assessed by measuring serum alanine aminotransfersase (ALT) and by histological examination of liver tissue sections. Results The absence of T cells (CD3εKO) is associated with significant protection from injury (p = 0.010). Through a strategy of antibody depletion it appears that NKT cells (p = 0.0025), rather than conventional T (CD4 + or CD8 +) (p = 0.11) cells that are the key mediators of injury. Discussion Our results indicate that tissue-resident NKT cells, but not other lymphocyte populations are responsible for the injury in hepatic IRI. Targeting the activation of NKT cells and/or their effector apparatus would be a novel approach in protecting the liver during transplantation and resection surgery; this may allow us to expand our current criteria for surgery. Highlights • Hepatic IRI worsens outcome in liver transplantation. • T cells are important in hepatic IRI. • These are tissue-resident rather than recruited T cells. • NKT, but not conventional T or NK cells, are key mediators of hepatic IRI. • Targeting NKT activation or their effector apparatus may offer therapeutic potential. |
| Databáze: | OpenAIRE |
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