PD-L1 is induced in hepatocytes by viral infection and by interferon-α and -γ and mediates T cell apoptosis
PD-L1 is induced in hepatocytes by viral infection and by interferon-α and -γ and mediates T cell apoptosis
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DOI：
10.1016/j.jhep.2006.05.007
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发表时间：
2006-10-01
影响因子：
25.7
通讯作者：
Hellerbrand, Claus
中科院分区：
文献类型：
--
作者：
Muehlbauer, Marcus;Fleck, Martin;Hellerbrand, Claus
背景/目的：B7-H1（PD-L1）是B7家族成员，与程序性死亡-1（PD-1）结合。最近，PD-L1的缺乏已被证明会导致实验性自身免疫性肝炎中加速的肝细胞损伤，并且PD-L1被认为在调节T细胞稳态中起关键作用。PD-1的缺乏增强了腺病毒感染肝脏中T细胞的增殖，并导致病毒的快速清除。在这里，我们的目的是得到更多的洞察肝脏PD-L1的表达，调节和function.Methods：PD-L1的表达进行了分析，通过定量PCR和流式细胞仪分析在原代人肝细胞和肝癌细胞。此外，与原代人T细胞或Jurkat T细胞共培养实验established.Results：除了非实质肝细胞，也肝细胞组成性表达低水平的PD-L1。肝细胞中的PD-L1表达通过活化的T细胞和病毒感染而强烈增强，并且通过I型或II型干扰素的进一步刺激而显著增强。此外，PD-L1在肝细胞上的表达诱导了T细胞的凋亡。结论：我们的研究结果表明，PD-L1在肝细胞中的表达调节了肝细胞和淋巴细胞之间的双向相互作用，这可能有助于肝脏独特的免疫学特性。(c)2006年欧洲肝脏研究协会。出版社：Elsevier B. V. All rights reserved.
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.