School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Republic of Ireland.
MRC Centre for Regenerative Medicine, University of Edinburgh, 5 Little France Drive, Edinburgh EH16 4UU, UK.
Philos Trans R Soc Lond B Biol Sci. 2018 Jul 5;373(1750). doi: 10.1098/rstb.2017.0220.
Stem cell-derived hepatocyte-like cells (HLCs) offer great opportunities for studies of host-pathogen interactions and tissue regeneration, as well as hepatotoxicity. To reliably predict the outcome of infection or to enhance graft survival, a finely tuned innate immune system is essential. Hepatocytes have long been considered solely metabolic and their critical innate immune potential is only recently gaining attention. Viral infection studies show that pathogen detection by cytosolic receptors leads to interferon (IFN) induction in primary hepatocytes and HLCs. IFN expression in HLCs is characterized by strong expression of type III IFN and low expression of type I IFN which is also a characteristic of primary hepatocytes. The response to IFN differs in HLCs with lower interferon-stimulated gene (ISG)-expression levels than in primary hepatocytes. Tumour necrosis factor-alpha (TNF-α) signalling is less studied in HLCs, but appears to be functional. Expression of toll-like receptors (TLR) 2-5, 7 and 9 has been reported in primary hepatocytes but has been poorly studied in HLCs. In summary, although they retain some immature features, HLCs are in many ways superior to hepatoma cell lines for cell-based modelling. In this review, we will provide an overview of innate immune signalling in HLCs and how this compares with primary hepatocytes.This article is part of the themed issue 'Designer human tissue: coming to a lab near you'.
干细胞来源的肝细胞样细胞 (HLCs) 为研究宿主-病原体相互作用和组织再生以及肝毒性提供了极好的机会。为了可靠地预测感染的结果或提高移植物的存活率，需要精细调节先天免疫系统。长期以来，肝细胞一直被认为仅具有代谢功能，其关键的先天免疫潜能最近才引起关注。病毒感染研究表明，细胞质受体对病原体的检测会导致原代肝细胞和 HLC 中干扰素 (IFN) 的诱导。HLC 中的 IFN 表达特征是强烈表达 III 型 IFN 和低表达 I 型 IFN，这也是原代肝细胞的特征。HLC 对 IFN 的反应不同于原代肝细胞，其干扰素刺激基因 (ISG) 表达水平较低。TNF-α 信号在 HLC 中的研究较少，但似乎是功能性的。已在原代肝细胞中报道了 Toll 样受体 (TLR) 2-5、7 和 9 的表达，但在 HLC 中研究甚少。总之，尽管它们保留了一些不成熟的特征，但在基于细胞的建模方面，HLC 在许多方面优于肝癌细胞系。在这篇综述中，我们将概述 HLC 中的先天免疫信号转导，以及与原代肝细胞的比较。本文是“设计人类组织：就在你附近的实验室”专题的一部分。
