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Expression of Inhibitory Receptors on T and NK Cells Defines Immunological Phenotypes of HCV Patients with Advanced Liver Fibrosis

Chronic HCV can result in advanced liver disease, including cirrhosis. Patients with advanced fibrosis experience poor clinical outcomes and increased risk for hepatocellular carcinoma (HCC). These outcomes are, in part, a consequence of immune dysfunction. Increased inhibitory receptor and Galectin...

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Autores principales: Okwor, Chisom Ifeoma Adaeze, Oh, Jun Seok, Crawley, Angela Marie, Cooper, Curtis Lindsey, Lee, Seung-Hwan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7492990/
https://www.ncbi.nlm.nih.gov/pubmed/32920488
http://dx.doi.org/10.1016/j.isci.2020.101513
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author Okwor, Chisom Ifeoma Adaeze
Oh, Jun Seok
Crawley, Angela Marie
Cooper, Curtis Lindsey
Lee, Seung-Hwan
author_facet Okwor, Chisom Ifeoma Adaeze
Oh, Jun Seok
Crawley, Angela Marie
Cooper, Curtis Lindsey
Lee, Seung-Hwan
author_sort Okwor, Chisom Ifeoma Adaeze
collection PubMed
description Chronic HCV can result in advanced liver disease, including cirrhosis. Patients with advanced fibrosis experience poor clinical outcomes and increased risk for hepatocellular carcinoma (HCC). These outcomes are, in part, a consequence of immune dysfunction. Increased inhibitory receptor and Galectin-9 (GAL-9) expression is a possible mechanism promoting lymphocyte dysfunction. In this study, we measured the expression of inhibitory receptors and GAL-9 on T/NK cells of patients with chronic HCV with no to moderate fibrosis (F0-F2) and advanced fibrosis (F3-F4). To analyze their co-expression, we employed t-SNE analysis. Notably, we found that F3-F4 patients had higher frequencies of >3 inhibitory receptor co-expression on NK cells. Moreover, F3-F4 patients manifest a higher frequency of NK cells co-expressing TIGIT and TIM-3, and CD4/NK cells co-expressing LAG-3 and GAL-9. In conclusion, we identified phenotypes of immune dysregulation that could explain the increased susceptibility to infection and HCC in patients with chronic HCV with advanced fibrosis.
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spelling pubmed-74929902020-09-24 Expression of Inhibitory Receptors on T and NK Cells Defines Immunological Phenotypes of HCV Patients with Advanced Liver Fibrosis Okwor, Chisom Ifeoma Adaeze Oh, Jun Seok Crawley, Angela Marie Cooper, Curtis Lindsey Lee, Seung-Hwan iScience Article Chronic HCV can result in advanced liver disease, including cirrhosis. Patients with advanced fibrosis experience poor clinical outcomes and increased risk for hepatocellular carcinoma (HCC). These outcomes are, in part, a consequence of immune dysfunction. Increased inhibitory receptor and Galectin-9 (GAL-9) expression is a possible mechanism promoting lymphocyte dysfunction. In this study, we measured the expression of inhibitory receptors and GAL-9 on T/NK cells of patients with chronic HCV with no to moderate fibrosis (F0-F2) and advanced fibrosis (F3-F4). To analyze their co-expression, we employed t-SNE analysis. Notably, we found that F3-F4 patients had higher frequencies of >3 inhibitory receptor co-expression on NK cells. Moreover, F3-F4 patients manifest a higher frequency of NK cells co-expressing TIGIT and TIM-3, and CD4/NK cells co-expressing LAG-3 and GAL-9. In conclusion, we identified phenotypes of immune dysregulation that could explain the increased susceptibility to infection and HCC in patients with chronic HCV with advanced fibrosis. Elsevier 2020-08-29 /pmc/articles/PMC7492990/ /pubmed/32920488 http://dx.doi.org/10.1016/j.isci.2020.101513 Text en © 2020 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Okwor, Chisom Ifeoma Adaeze
Oh, Jun Seok
Crawley, Angela Marie
Cooper, Curtis Lindsey
Lee, Seung-Hwan
Expression of Inhibitory Receptors on T and NK Cells Defines Immunological Phenotypes of HCV Patients with Advanced Liver Fibrosis
title Expression of Inhibitory Receptors on T and NK Cells Defines Immunological Phenotypes of HCV Patients with Advanced Liver Fibrosis
title_full Expression of Inhibitory Receptors on T and NK Cells Defines Immunological Phenotypes of HCV Patients with Advanced Liver Fibrosis
title_fullStr Expression of Inhibitory Receptors on T and NK Cells Defines Immunological Phenotypes of HCV Patients with Advanced Liver Fibrosis
title_full_unstemmed Expression of Inhibitory Receptors on T and NK Cells Defines Immunological Phenotypes of HCV Patients with Advanced Liver Fibrosis
title_short Expression of Inhibitory Receptors on T and NK Cells Defines Immunological Phenotypes of HCV Patients with Advanced Liver Fibrosis
title_sort expression of inhibitory receptors on t and nk cells defines immunological phenotypes of hcv patients with advanced liver fibrosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7492990/
https://www.ncbi.nlm.nih.gov/pubmed/32920488
http://dx.doi.org/10.1016/j.isci.2020.101513
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