ArticlePloS one2014
Functions of liver natural killer cells are dependent on the severity of liver inflammation and fibrosis in chronic hepatitis C.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 26 citations in OpenAlex.
- Differences in the intrahepatic expression of immune checkpoint molecules on T cells and natural killer cells in chronic HBV patients.Frontiers in immunology · 2024Article
- Association of NK Cells with the Severity of Fibrosis in Patients with Chronic Hepatitis C.Diagnostics (Basel, Switzerland) · 2023Article
- Etiology of end-stage liver cirrhosis impacts hepatic natural killer cell heterogenicity.Frontiers in immunology · 2023Article
- The antifibrotic role of natural killer cells in liver fibrosis.Experimental biology and medicine (Maywood, N.J.) · 2022Review
- Crosstalk between NK cells and hepatic stellate cells in liver fibrosis (Review).Molecular medicine reports · 2022Review
- Inflammation response and liver stiffness: predictive model of regression of hepatic stiffness after sustained virological response in cirrhotics patients with chronic hepatitis C.Clinical and experimental medicine · 2021Article
- Increased Intrahepatic Expression of Immune Checkpoint Molecules in Autoimmune Liver Disease.Cells · 2021Article
- Emerging roles and mechanisms of microRNA‑222‑3p in human cancer (Review).International journal of oncology · 2021Review
- Article
- Review
- Insulin signaling as a potential natural killer cell checkpoint in fatty liver disease.Hepatology communications · 2018Article
- Hepatic Immune Microenvironment in Alcoholic and Nonalcoholic Liver Disease.BioMed research international · 2017Review
- Sex Differences in Spontaneous Degranulation Activity of Intrahepatic Natural Killer Cells during Chronic Hepatitis B: Association with Estradiol Levels.Mediators of inflammation · 2017Article
- NK cell function and receptor diversity in the context of HCV infection.Frontiers in microbiology · 2015Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
During chronic hepatitis C virus (HCV) infection, the role of intra-hepatic (IH) natural killer (NK) cells is still controversial. To clarify their functions, we investigated anti-viral and cytotoxic activity of NK cells in human fresh liver biopsies. We compared the functions of IH-NK cells in HCV-infected and NASH patients in physiological conditions as well as after stimulation using flow cytometric and immunohistochemical analyses. Interestingly, few IH-NK cells produced anti-viral cytokine IFN-γ in HCV-infected patients similarly as in non-infected individuals. Spontaneous degranulation activity was extremely low in peripheral NK cells compared to IH-NK cells, and was significantly higher in IH-NK cells from HCV-infected patients compared to non-infected individuals. Immunohistochemical analysis revealed that perforin granules were polarized at the apical pole of IH-NK cells. The presence of CD107a and perforin in IH-NK cells demonstrated that NK cells exerted a cytolytic activity at the site of infection. Importantly, IH-NK cell functions from HCV-infected patients were inducible by specific exogenous stimulations. Upon ex vivo K562 target cell stimulations, the number of degranulating NK cells was significantly increased in the pool of IH-NK cells compared to circulating NK cells. Interestingly, after stimulation, the frequency of IFN-γ-producing IH-NK cells in HCV-infected patients was significantly higher at early stage of inflammation whereas the spontaneous IH-NK cell degranulation activity was significantly impaired in patients with highest inflammation and fibrosis Metavir scores. Our study highlights that some IH-NK cells in HCV-infected patients are able to produce INF-γ and degranulate and that those two activities depend on liver environment including the severity of liver injury. Thus, we conclude that critical roles of IH-NK cells have to be taken into account in the course of the liver pathogenesis associated to chronic HCV infection.
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