期刊
JOURNAL OF INNATE IMMUNITY
卷 10, 期 4, 页码 339-348出版社
KARGER
DOI: 10.1159/000489966
关键词
Checkpoint inhibitors; Hepatic stellate cell; Host defense; Kupffer cell; Liver sinusoidal endothelial cells; Macrophages; Pathogen-associated molecular patterns; Pattern recognition receptors; Primary cells; Primary human hepatocytes
类别
资金
- INSERM
- ANRS
- DEVweCAN LABEX [ANR-10-LABX-0061]
- FINOVI foundation
Different liver cell types are endowed with immunological properties, including cell-intrinsic innate immune functions that are important to initially control pathogen infections. However, a full landscape of expression and functionality of the innate immune signaling pathways in the major human liver cells is still missing. In order to comparatively characterize these pathways, we purified primary human hepatocytes, hepatic stellate cells, liver sinusoidal endothelial cells (LSEC), and Kupffer cells (KC) from human liver resections. We assessed mRNA and protein expression level of the major innate immune sensors, as well as checkpoint-inhibitor ligands in the purified cells, and found Toll-like receptors (TLR), RIG-I-like receptors, as well as several DNA cytosolic sensors to be expressed in the liver microenvironment. Amongst the cells tested, KC were shown to be most broadly active upon stimulation with PRR ligands emphasizing their predominant role in innate immune sensing the liver microenvironment. By KC immortalization, we generated a cell line that retained higher innate immune functionality as compared to THP1 cells, which are routinely used to study monocyte/macrophages functions. Our findings and the establishment of the KC line will help to understand immune mechanisms behind antiviral effects of TLR agonists or checkpoint inhibitors, which are in current preclinical or clinical development. (C) 2018 S. Karger AG, Basel
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