Soleimani Shaghayegh, Albayrak Ozgur, Somay Kayra, Yang Hong, Yigit Buket, Ulukan Burge, Atak Dila, Akyildiz Murat, Gursoy Metehan, Demirtas Elif, Mardinoglu Adil, Vural Atay, Dayangac Murat, Zeybel Mujdat
Koç University Research Center for Translational Medicine (KUTTAM), Koç University, Istanbul, Türkiye.
Department of Gastroenterology and Hepatology, School of Medicine, Koç University, Istanbul, Türkiye.
Front Mol Biosci. 2025 Jan 29;11:1521811. doi: 10.3389/fmolb.2024.1521811. eCollection 2024.
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.
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.
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 and upregulation of in ARLD, consistent with a highly differentiated phenotype. and were upregulated in peri-tumor samples. The NK cell count was lower in peri-tumor liver specimens compared to ARLD, and an upregulation of , an inhibitory marker, was observed in those peri-tumor specimens.
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.
酒精性肝病和慢性病毒性肝炎所致的慢性肝病给医疗系统带来了沉重负担。慢性肝病可能易引发肝细胞癌，而其治疗选择有限。本研究旨在探索这些临床病症的免疫细胞特征。
收集25例患者的肝外植体样本进行批量RNA测序和流式细胞术分析。通过流式细胞术对分离出的肝和外周血单个核细胞中的免疫细胞群体进行表征。
在三种临床病症的患者中观察到免疫细胞特征存在显著差异。与酒精性肝病相比，病毒性肝炎和肿瘤周边样本的肝B细胞计数更高。此外，慢性肝病患者的CD57 T细胞水平更高，提示T细胞分化。差异表达分析确定了几个与免疫调节相关的基因，包括酒精性肝病中[基因名称1]的下调和[基因名称2]的上调，这与高度分化的表型一致。[基因名称3]和[基因名称4]在肿瘤周边样本中上调。与酒精性肝病相比，肿瘤周边肝标本中的自然杀伤细胞计数较低，并且在那些肿瘤周边标本中观察到抑制性标志物[基因名称5]的上调。
本研究有助于理解不同病因的慢性肝病中的免疫动态。与其他组相比，酒精性肝病中的B淋巴细胞相对减少，并且T细胞表现出更分化的亚型。肝癌的肿瘤周边微环境表明自然杀伤细胞的存在相对减少，并且有潜在的抑制特性增加的趋势。
