PD-L1 is induced in hepatocytes by viral infection and by interferon-alpha and -gamma and mediates T cell apoptosis

Muehlbauer, Marcus and Fleck, Martin and Schuetz, Christian and Weiss, Thomas and Froh, Matthias and Blank, Christian and Schoelmerich, Juergen and Hellerbrand, Claus (2006) PD-L1 is induced in hepatocytes by viral infection and by interferon-alpha and -gamma and mediates T cell apoptosis. JOURNAL OF HEPATOLOGY, 45 (4). pp. 520-528. ISSN 0168-8278,

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Abstract

Background/Aims:B7-H1 (PD-L1) is a B7-family member that binds to programmed death-1 (PD-1). Recently, deficiency of PD-L1 has been demonstrated to result in accelerated hepatocyte damage in experimental autoimmune hepatitis, and PD-L1 was suggested to play a critical role in regulating T cell homeostasis. Absence of PD-1 enhanced proliferation of T cells in adenovirus-infected livers and resulted in a rapid clearance of the virus. Here, we aimed to get more insight into hepatic PD-L1 expression, regulation and function. Methods: PD-L1 expression was analyzed by quantitative PCR and FACS-analysis in primary human liver cells and hepatoma cells. Furthermore, coculture experiments with primary human T cells or Jurkat T cells were established. Results: In addition to nonparenchymal liver cells, also hepatocytes constitutively expressed low levels of PD-L1. PD-L1 expression in hepatocytes was strongly enhanced by activated T cells and viral infection, and markedly augmented by further stimulation with type I or type II interferons. Moreover, PD-L1 expression on hepatocytes induced apoptosis in T cells. Conclusions: Our results suggest a novel bidirectional interaction between hepatocytes and lymphocytes modulated by PD-L1 expression in hepatocytes, which may contribute to the unique immunological properties of the liver. (c) 2006 European Association for the Study of the Liver. Published by Elsevier B.V.. All rights reserved.

Item Type: Article
Uncontrolled Keywords: HEPATIC STELLATE CELLS; NECROSIS-FACTOR-ALPHA; C VIRUS-INFECTION; ENDOTHELIAL-CELLS; DENDRITIC CELLS; TRANSGENIC MICE; IMMUNE EVASION; B7 FAMILY; EXPRESSION; B7-H1; PD-L1; B7-H1; PD-1; apoptosis; liver; hepatocytes; tolerance
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Chirurgie
Medicine > Lehrstuhl für Innere Medizin I
Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie)
Depositing User: Dr. Gernot Deinzer
Date Deposited: 25 Jan 2021 09:40
Last Modified: 25 Jan 2021 09:40
URI: https://pred.uni-regensburg.de/id/eprint/33953

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