Single-cell RNA transcriptomics reveals differences in the immune status of alcoholic and hepatitis B virus-related liver cirrhosis.
Single-cell RNA transcriptomics reveals differences in the immune status of alcoholic and hepatitis B virus-related liver cirrhosis.
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DOI：
10.3389/fendo.2023.1132085
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发表时间：
2023
影响因子：
5.2
通讯作者：
中科院分区：
文献类型：
--
作者：
酒精和B型肝炎病毒（HBV）相关的肝硬化给医疗保健系统带来了巨大的负担，治疗选择有限。本研究旨在探讨酒精性肝硬化与乙型肝炎肝硬化患者免疫状态的差异。共使用来自中南大学湘雅三医院的15份人类肝脏样本，包括5名健康对照（HC组）、5名酒精性肝硬化患者（ALC组）和5名HBV相关肝硬化患者（HBV组）。其中，随机收集8份样本，包括3份HC组，2份ALC组和3份HBV组，进行单细胞RNA测序（scRNA-seq）。通过H&E染色评估脂肪变性的程度，并通过免疫化学（IHC）评估肝内免疫细胞的存在。酒精性肝硬化和乙型肝炎相关肝硬化的免疫状态差异显着。ScRNA-seq分析发现ALC组中肝内单核细胞/巨噬细胞的比例高于HBV组，而T细胞和B细胞的比例明显降低。肝内单核细胞/巨噬细胞、T和B细胞的IHC染色显示与scRNA-seq分析相似的结果。CD 5L + Kupffer细胞是ALC肝组织中主要的单核/巨噬细胞亚群，是一种参与脂质代谢的细胞类型。H&E染色显示ALC组的脂肪变性程度较HBV组严重。配体/受体分析表明，在ALC肝脏中观察到的T细胞耗竭可能与枯否细胞上半乳糖凝集素-9的表达有关。在ALC组中也发现了较少的B细胞，并且大多数具有较高的脂质代谢、降低的核糖体活性和失调的线粒体氧化磷酸化系统。此外，scRNA-seq显示血浆B细胞的比率显著较低，表明ALC肝脏中的体液免疫应答类似地功能失调。配体/受体分析还发现Kupffer细胞上表达的Galectin-9可抑制体液免疫。ALC患者与HBV诱导的肝硬化患者具有不同的免疫特征，包括肝内单核细胞/巨噬细胞比例增加和肝脏适应性免疫应答功能障碍。Galectin-9可能作为ALC治疗的潜在治疗靶点。
Alcoholic and hepatitis B virus (HBV)-related liver cirrhosis has placed a tremendous burden on the healthcare system with limited treatment options. This study explored the differences in the immune status of alcoholic and HBV-related liver cirrhosis. A total of 15 human liver samples from the Third Xiangya Hospital of Central South University, including five healthy controls (HC group), five alcoholic cirrhosis patients (ALC group), and five HBV-related cirrhosis patients (HBV group) were used. Of these, eight samples, including 3 HC group, 2 ALC group and 3 HBV group, were randomly collected to do single-cell RNA sequencing (scRNA-seq). The degree of steatosis was assessed by H&E staining and the presence of intrahepatic immune cells was evaluated by immunochemistry (IHC). The immune status of alcoholic and HBV-related liver cirrhosis differed significantly. ScRNA-seq analysis identified a higher ratio of intrahepatic monocyte/macrophages and an obvious decreased ratio of T cells and B cells in the ALC group than in the HBV group. IHC staining of intrahepatic monocyte/macrophages, T and B cell exhibited similar results with scRNA-seq analysis. CD5L+ Kupffer cells, a cell type involved in lipid metabolism, were the major monocyte/macrophage subset in ALC liver tissue. H&E staining indicated that the level of steatosis was more severe in the ALC than in the HBV group. Ligand/receptor analysis showed that the T cell exhaustion observed in the ALC liver may be related to the expression of Galectin-9 on Kupffer cells. Fewer B cells were also found in the ALC group and most had higher lipid metabolism, reduced ribosomal activity, and a dysregulated mitochondrial oxidative phosphorylation system. Moreover, scRNA-seq showed a significantly lower ratio of plasma B cells, indicating that the humoral immune response in the ALC liver was similarly dysfunctional. Ligand/receptor analysis also discovered that Galectin-9 expressed on Kupffer cells may inhibit humoral immunity. Patients with ALC have different immune characteristics than those with HBV-induced cirrhosis, including an increased ratio of intrahepatic monocyte/macrophages and a dysfunctional adaptive immune response in the liver. Galectin-9 could serve as a potential therapeutic target for ALC treatment.
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影响因子：
30.5
作者：
Arazi, Arnon;Rao, Deepak A.;Goldman, Daniel H.
通讯作者：
Goldman, Daniel H.
影响因子：
3.7
作者：
Cho YE;Im EJ;Moon PG;Mezey E;Song BJ;Baek MC
通讯作者：
Baek MC
DOI：
10.1111/j.1440-1746.2006.04650.x
发表时间：
2007-06-01
影响因子：
4.1
作者：
Thakur, Varsha;McMullen, Megan R.;Nagy, Laura E.
通讯作者：
Nagy, Laura E.
影响因子：
1.2
作者：
Kegel, Victoria;Deharde, Daniela;Damm, Georg
通讯作者：
Damm, Georg
影响因子：
2.4
作者：
Matos, Luis Costa;Batista, Paulo;Carvalho, Armando
通讯作者：
Carvalho, Armando