Cellular and immune landscape of chronic liver diseases: insights from immunophenotyping

BackgroundChronic liver disease due to alcohol-related liver disease and chronic viral hepatitis pose a substantial burden on healthcare systems. Chronic liver disease may predispose to hepatocellular carcinoma, for which therapeutic options are limited. This study aimed to explore the immune cell c...

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Main Authors: Shaghayegh Soleimani, Ozgur Albayrak, Kayra Somay, Hong Yang, Buket Yigit, Burge Ulukan, Dila Atak, Murat Akyildiz, Metehan Gursoy, Elif Demirtas, Adil Mardinoglu, Atay Vural, Murat Dayangac, Mujdat Zeybel
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-01-01
Series:Frontiers in Molecular Biosciences
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Online Access:https://www.frontiersin.org/articles/10.3389/fmolb.2024.1521811/full
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author Shaghayegh Soleimani
Shaghayegh Soleimani
Ozgur Albayrak
Kayra Somay
Hong Yang
Buket Yigit
Burge Ulukan
Dila Atak
Murat Akyildiz
Metehan Gursoy
Elif Demirtas
Adil Mardinoglu
Adil Mardinoglu
Atay Vural
Atay Vural
Murat Dayangac
Mujdat Zeybel
author_facet Shaghayegh Soleimani
Shaghayegh Soleimani
Ozgur Albayrak
Kayra Somay
Hong Yang
Buket Yigit
Burge Ulukan
Dila Atak
Murat Akyildiz
Metehan Gursoy
Elif Demirtas
Adil Mardinoglu
Adil Mardinoglu
Atay Vural
Atay Vural
Murat Dayangac
Mujdat Zeybel
author_sort Shaghayegh Soleimani
collection DOAJ
description BackgroundChronic liver disease due to alcohol-related liver disease and chronic viral hepatitis pose a substantial burden on healthcare systems. Chronic liver disease may predispose to hepatocellular carcinoma, for which therapeutic options are limited. This study aimed to explore the immune cell characteristics of the clinical conditions.MethodsExplant liver samples were collected from 25 patients for bulk RNA sequencing and flow cytometry analysis. Immune cell populations were characterized by flow cytometry from isolated hepatic and peripheral mononuclear cells.ResultsSignificant differences in immune cell characteristics were observed among patients with three clinical conditions. Viral hepatitis and peri-tumor samples exhibited higher hepatic B cell counts compared to alcohol-related liver disease. Additionally, chronic liver disease patients showed higher levels of CD57+ T cells, suggestive of T cell differentiation. Differential expression analysis identified several genes associated with immune regulation, including downregulation of CD27 and upregulation of granzyme B in ARLD, consistent with a highly differentiated phenotype. LAG3 and PDCD1 were upregulated in peri-tumor samples. The NK cell count was lower in peri-tumor liver specimens compared to ARLD, and an upregulation of TIGIT, an inhibitory marker, was observed in those peri-tumor specimens.ConclusionThis study contributes to the understanding of immune dynamics in chronic liver disease among different etiologies. B lymphocytes are relatively reduced in alcohol-related liver disease compared to other groups, and T cells exhibit a more differentiated subtype. The peritumor microenvironment in HCC suggests a relatively diminished presence of NK cells and a potential tendency toward increased inhibitory characteristics.
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spelling doaj-art-0de4bd384dff4aa4b323a76ce263d23f2025-01-29T05:21:27ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2025-01-011110.3389/fmolb.2024.15218111521811Cellular and immune landscape of chronic liver diseases: insights from immunophenotypingShaghayegh Soleimani0Shaghayegh Soleimani1Ozgur Albayrak2Kayra Somay3Hong Yang4Buket Yigit5Burge Ulukan6Dila Atak7Murat Akyildiz8Metehan Gursoy9Elif Demirtas10Adil Mardinoglu11Adil Mardinoglu12Atay Vural13Atay Vural14Murat Dayangac15Mujdat Zeybel16Koç University Research Center for Translational Medicine (KUTTAM), Koç University, Istanbul, TürkiyeDepartment of Gastroenterology and Hepatology, School of Medicine, Koç University, Istanbul, TürkiyeKoç University Research Center for Translational Medicine (KUTTAM), Koç University, Istanbul, TürkiyeDepartment of Internal Medicine, School of Medicine, Koç University, Istanbul, TürkiyeScience for Life Laboratory, KTH - Royal Institute of Technology, Stockholm, SwedenDepartment of Gastroenterology and Hepatology, School of Medicine, Koç University, Istanbul, TürkiyeDepartment of Gastroenterology and Hepatology, School of Medicine, Koç University, Istanbul, TürkiyeDepartment of Gastroenterology and Hepatology, School of Medicine, Koç University, Istanbul, TürkiyeDepartment of Gastroenterology and Hepatology, School of Medicine, Koç University, Istanbul, TürkiyeDepartment of Internal Medicine, School of Medicine, Koç University, Istanbul, TürkiyeDepartment of Internal Medicine, School of Medicine, Koç University, Istanbul, TürkiyeScience for Life Laboratory, KTH - Royal Institute of Technology, Stockholm, SwedenCentre for Host-Microbiome Interactions, Faculty of Dentistry, Oral and Craniofacial Sciences, King’s College London, London, United KingdomKoç University Research Center for Translational Medicine (KUTTAM), Koç University, Istanbul, TürkiyeDepartment of Neurology, School of Medicine, Koc University, Istanbul, TürkiyeDepartment of General Surgery, Medipol University, Istanbul, TürkiyeDepartment of Gastroenterology and Hepatology, School of Medicine, Koç University, Istanbul, TürkiyeBackgroundChronic liver disease due to alcohol-related liver disease and chronic viral hepatitis pose a substantial burden on healthcare systems. Chronic liver disease may predispose to hepatocellular carcinoma, for which therapeutic options are limited. This study aimed to explore the immune cell characteristics of the clinical conditions.MethodsExplant liver samples were collected from 25 patients for bulk RNA sequencing and flow cytometry analysis. Immune cell populations were characterized by flow cytometry from isolated hepatic and peripheral mononuclear cells.ResultsSignificant differences in immune cell characteristics were observed among patients with three clinical conditions. Viral hepatitis and peri-tumor samples exhibited higher hepatic B cell counts compared to alcohol-related liver disease. Additionally, chronic liver disease patients showed higher levels of CD57+ T cells, suggestive of T cell differentiation. Differential expression analysis identified several genes associated with immune regulation, including downregulation of CD27 and upregulation of granzyme B in ARLD, consistent with a highly differentiated phenotype. LAG3 and PDCD1 were upregulated in peri-tumor samples. The NK cell count was lower in peri-tumor liver specimens compared to ARLD, and an upregulation of TIGIT, an inhibitory marker, was observed in those peri-tumor specimens.ConclusionThis study contributes to the understanding of immune dynamics in chronic liver disease among different etiologies. B lymphocytes are relatively reduced in alcohol-related liver disease compared to other groups, and T cells exhibit a more differentiated subtype. The peritumor microenvironment in HCC suggests a relatively diminished presence of NK cells and a potential tendency toward increased inhibitory characteristics.https://www.frontiersin.org/articles/10.3389/fmolb.2024.1521811/fullchronic liver diseasehepatitisliver immunophenotypinghepatic inflammationfibrosis
spellingShingle Shaghayegh Soleimani
Shaghayegh Soleimani
Ozgur Albayrak
Kayra Somay
Hong Yang
Buket Yigit
Burge Ulukan
Dila Atak
Murat Akyildiz
Metehan Gursoy
Elif Demirtas
Adil Mardinoglu
Adil Mardinoglu
Atay Vural
Atay Vural
Murat Dayangac
Mujdat Zeybel
Cellular and immune landscape of chronic liver diseases: insights from immunophenotyping
Frontiers in Molecular Biosciences
chronic liver disease
hepatitis
liver immunophenotyping
hepatic inflammation
fibrosis
title Cellular and immune landscape of chronic liver diseases: insights from immunophenotyping
title_full Cellular and immune landscape of chronic liver diseases: insights from immunophenotyping
title_fullStr Cellular and immune landscape of chronic liver diseases: insights from immunophenotyping
title_full_unstemmed Cellular and immune landscape of chronic liver diseases: insights from immunophenotyping
title_short Cellular and immune landscape of chronic liver diseases: insights from immunophenotyping
title_sort cellular and immune landscape of chronic liver diseases insights from immunophenotyping
topic chronic liver disease
hepatitis
liver immunophenotyping
hepatic inflammation
fibrosis
url https://www.frontiersin.org/articles/10.3389/fmolb.2024.1521811/full
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