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A subset of liver resident natural killer cells is expanded in hepatitis C-infected patients with better liver function.
- Source :
-
Scientific reports [Sci Rep] 2021 Jan 15; Vol. 11 (1), pp. 1551. Date of Electronic Publication: 2021 Jan 15. - Publication Year :
- 2021
-
Abstract
- Viral hepatitis leads to immune-mediated liver injury. The rate of disease progression varies between individuals. We aimed to phenotype immune cells associated with preservation of normal liver function during hepatitis C virus (HCV) infection. Clinical data and specimens were obtained from 19 HCV-infected patients undergoing liver transplantation. Liver and peripheral blood mononuclear cells were isolated and eight subsets of innate immune cells were delineated by multiparameter flow cytometry. Cytokine assays and microarrays were performed. Intrahepatic CD56 <superscript>Bright</superscript> /CD16 <superscript>-</superscript> natural killer (NK) cells comprised the only subset correlating with better liver function, i.e., lower bilirubin (p = 0.0002) and lower model for end stage of liver disease scores (p = 0.03). The signature of liver NK cells from HCV-infected patients included genes expressed by NK cells in normal liver and by decidual NK cells. Portal vein blood had a higher concentration of interleukin (IL)-10 than peripheral blood (p = 0.03). LMCs were less responsive to toll-like receptor (TLR) stimulation than PBMCs, with fewer pro-inflammatory gene-expression pathways up-regulated after in vitro exposure to lipopolysaccharide and a TLR-7/8 agonist. Hepatic CD56 <superscript>Bright</superscript> /CD16 <superscript>-</superscript> NK cells may be critical for maintaining liver homeostasis. Portal vein IL-10 may prime inhibitory pathways, attenuating TLR signaling and reducing responsiveness to pro-inflammatory stimuli.
- Subjects :
- Aged
Disease Progression
Female
Flow Cytometry methods
Hepacivirus pathogenicity
Hepatitis C metabolism
Hepatitis C physiopathology
Humans
Immunity, Innate immunology
Immunity, Innate physiology
Immunophenotyping
Killer Cells, Natural pathology
Leukocytes, Mononuclear metabolism
Liver immunology
Liver Function Tests methods
Male
Middle Aged
Hepatitis C immunology
Killer Cells, Natural metabolism
Liver pathology
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 11
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 33452360
- Full Text :
- https://doi.org/10.1038/s41598-020-80819-8