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ORIGINAL RESEARCH article
Front. Mol. Biosci.
Sec. Molecular Diagnostics and Therapeutics
Volume 11 - 2024 |
doi: 10.3389/fmolb.2024.1521811
This article is part of the Research Topic Exploring Molecular Recognition: Integrating Experimental and Computational Approaches View all 3 articles
Cellular and Immune Landscape of Chronic Liver Diseases: Insights from Immunophenotyping
Provisionally accepted
Özgür Albayrak
1
Shaghayegh Soleimani
2
Kayra Somay
2
Hong Yang
3
Buket Yigit
2
Burge Ulukan
2
Dila Atak
2
Murat Akyildiz
2
Metehan Gursoy
2
Elif Demirtas
2
Adil Mardinoglu
3
Atay Vural
2
Murat Dayangaç
4
Mujdat Zeybel
2*- 1 KUTTAM, Koç University, Istanbul, Türkiye
- 2 Koç University, Istanbul, Türkiye
- 3 Royal Institute of Technology, Stockholm, Stockholm, Sweden
- 4 Istanbul Medipol University, Istanbul, Türkiye
Background: Chronic 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. Methods: Explant 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. Results: Significant 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. Conclusion: This 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.
Keywords: chronic liver disease, Hepatitis, Liver immunophenotyping, Hepatic inflammation, Fibrosis
Received: 02 Nov 2024; Accepted: 27 Dec 2024.
Copyright: © 2024 Albayrak, Soleimani, Somay, Yang, Yigit, Ulukan, Atak, Akyildiz, Gursoy, Demirtas, Mardinoglu, Vural, Dayangaç and Zeybel. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Mujdat Zeybel, Koç University, Istanbul, Türkiye
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