Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand on NK Cells Protects From Hepatic Ischemia-Reperfusion Injury

Fahrner, René; Trochsler, Markus; Corazza, Nadia; Graubardt, Nadine; Keogh, Adrian; Candinas, Daniel; Brunner, Thomas; Keogh-Stroka, Deborah M.; Beldi, Guido (2014). Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand on NK Cells Protects From Hepatic Ischemia-Reperfusion Injury. Transplantation, 97(11), pp. 1102-1109. Lippincott Williams & Wilkins 10.1097/TP.0000000000000101

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BACKGROUND: Ischemia-reperfusion injury (IRI) significantly contributes to graft dysfunction after liver transplantation. Natural killer (NK) cells are crucial innate effector cells in the liver and express tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a potent inducer of hepatocyte cell death. Here, we investigated if TRAIL expression on NK cells contributes to hepatic IRI. METHODS: The outcome after partial hepatic IRI was assessed in TRAIL-null mice and contrasted to C57BL/6J wild-type mice and after NK cell adoptive transfer in RAG2/common gamma-null mice that lack T, B, and NK cells. Liver IRI was assessed by histological analysis, alanine aminotransferase, hepatic neutrophil activation by myeloperoxidase activity, and cytokine secretion at specific time points. NK cell cytotoxicity and differentiation were assessed in vivo and in vitro. RESULTS: Twenty-four hours after reperfusion, TRAIL-null mice exhibited significantly higher serum transaminases, histological signs of necrosis, neutrophil infiltration, and serum levels of interleukin-6 compared to wild-type animals. Adoptive transfer of TRAIL-null NK cells into immunodeficient RAG2/common gamma-null mice was associated with significantly elevated liver damage compared to transfer of wild-type NK cells. In TRAIL-null mice, NK cells exhibit higher cytotoxicity and decreased differentiation compared to wild-type mice. In vitro, cytotoxicity against YAC-1 and secretion of interferon gamma by TRAIL-null NK cells were significantly increased compared to wild-type controls. CONCLUSIONS: These experiments reveal that expression of TRAIL on NK cells is protective in a murine model of hepatic IRI through modulation of NK cell cytotoxicity and NK cell differentiation.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Viszeralchirurgie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Viszeralchirurgie

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Visceral Surgery
04 Faculty of Medicine > Service Sector > Institute of Pathology > Immunopathology
04 Faculty of Medicine > Service Sector > Institute of Pathology

UniBE Contributor:

Fahrner, René; Trochsler, Markus; Corazza, Nadia; Graubardt, Nadine; Keogh, Adrian; Candinas, Daniel; Keogh-Stroka, Deborah M. and Beldi, Guido

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

0041-1337

Publisher:

Lippincott Williams & Wilkins

Language:

English

Submitter:

Lilian Karin Smith-Wirth

Date Deposited:

16 Apr 2015 12:16

Last Modified:

17 Jun 2015 02:30

Publisher DOI:

10.1097/TP.0000000000000101

PubMed ID:

24804996

Uncontrolled Keywords:

NK cells, Tumor necrosis factor-related apoptosis-inducing ligand, Hepatic ischemia-reperfusion injury, NK cell maturation, Cytotoxicity.

BORIS DOI:

10.7892/boris.65411

URI:

https://boris.unibe.ch/id/eprint/65411

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