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Characterization of pattern recognition receptor expression and functionality in liver primary cells and derived cell lines.
J. Innate Immun. 10, 339–348 (2018)
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter 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; Hepatitis-b-virus; Innate Immune-response; Agonist Gs-9620; Tissue; Hepatocytes; Immunotherapy; Macrophages; Combination; Homeostasis; Infections
ISSN (print) / ISBN 1662-811X
Zeitschrift Journal of Innate Immunity
Quellenangaben Band: 10, Heft: 4, Seiten: 339–348
Verlagsort Allschwilerstrasse 10, Ch-4009 Basel, Switzerland
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Virology (VIRO)