A subset of liver resident natural killer cells is expanded in hepatitis C-infected patients with better liver function

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 fro...

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Autores principales: Erin H. Doyle, Costica Aloman, Ahmed El-Shamy, Francis Eng, Adeeb Rahman, Arielle L. Klepper, Brandy Haydel, Sander S. Florman, M. Isabel Fiel, Thomas Schiano, Andrea D. Branch
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Publicado: Nature Portfolio 2021
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spelling oai:doaj.org-article:a26e3fb007f44f6b928d328f7069b4222021-12-02T14:01:22ZA subset of liver resident natural killer cells is expanded in hepatitis C-infected patients with better liver function10.1038/s41598-020-80819-82045-2322https://doaj.org/article/a26e3fb007f44f6b928d328f7069b4222021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-80819-8https://doaj.org/toc/2045-2322Abstract 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 CD56Bright/CD16- 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 CD56Bright/CD16- 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.Erin H. DoyleCostica AlomanAhmed El-ShamyFrancis EngAdeeb RahmanArielle L. KlepperBrandy HaydelSander S. FlormanM. Isabel FielThomas SchianoAndrea D. BranchNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Erin H. Doyle
Costica Aloman
Ahmed El-Shamy
Francis Eng
Adeeb Rahman
Arielle L. Klepper
Brandy Haydel
Sander S. Florman
M. Isabel Fiel
Thomas Schiano
Andrea D. Branch
A subset of liver resident natural killer cells is expanded in hepatitis C-infected patients with better liver function
description 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 CD56Bright/CD16- 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 CD56Bright/CD16- 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.
format article
author Erin H. Doyle
Costica Aloman
Ahmed El-Shamy
Francis Eng
Adeeb Rahman
Arielle L. Klepper
Brandy Haydel
Sander S. Florman
M. Isabel Fiel
Thomas Schiano
Andrea D. Branch
author_facet Erin H. Doyle
Costica Aloman
Ahmed El-Shamy
Francis Eng
Adeeb Rahman
Arielle L. Klepper
Brandy Haydel
Sander S. Florman
M. Isabel Fiel
Thomas Schiano
Andrea D. Branch
author_sort Erin H. Doyle
title A subset of liver resident natural killer cells is expanded in hepatitis C-infected patients with better liver function
title_short A subset of liver resident natural killer cells is expanded in hepatitis C-infected patients with better liver function
title_full A subset of liver resident natural killer cells is expanded in hepatitis C-infected patients with better liver function
title_fullStr A subset of liver resident natural killer cells is expanded in hepatitis C-infected patients with better liver function
title_full_unstemmed A subset of liver resident natural killer cells is expanded in hepatitis C-infected patients with better liver function
title_sort subset of liver resident natural killer cells is expanded in hepatitis c-infected patients with better liver function
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/a26e3fb007f44f6b928d328f7069b422
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