Role of HBeAg-induced immune activition and immunosuppression in chronic hepatitis B

Xinyang LI; Zhengkun TU

doi:10.12449/JCH240525

Volume 40 Issue 5

May 2024

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Article Navigation > Journal of Clinical Hepatology > 2024 > 40(5): 1026-1031

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Role of HBeAg-induced immune activition and immunosuppression in chronic hepatitis B

DOI: 10.12449/JCH240525

Xinyang LI,
Zhengkun TU^{,
,}

Laboratory of Tumor Immunology，The First Hospital of Jilin University，Changchun 130021，China

Research funding:

Jilin Province Science and Technology Development Plan Project Natural Science Foundation Project (20190201245JC)

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Corresponding author: TU Zhengkun， tuzhengkun@hotmail.com （ORCID： 0000-0001-6803-2015）
Received Date: 2024-01-25
Accepted Date: 2024-02-22
Published Date: 2024-05-25

Abstract

Abstract

Chronic hepatitis B induced by HBV infection is a significant risk factor leading to liver cirrhosis and liver cancer. Half a century ago， HBeAg was first discovered in the serum of HBV infected individuals， and although HBeAg does not participate in HBV infection or replication in hepatocytes， studies have shown that it can interfere with the innate and adaptive immune responses of the host and play an important role in immune activation and immunosuppression during chronic HBV infection. HBV has no cytotoxicity to the infected hepatocytes， and the antiviral action and inflammatory response mediated by immune response determine whether HBV is cleared or induces liver inflammation-related diseases. Therefore， this article reviews the formation of HBeAg and its immune activation and immunosuppression mechanisms in chronic HBV infection， with a focus on the different immune effects caused by HBeAg on innate immune and adaptive immune cells， and this article also elaborates on the dual role of HBeAg in inducing immune responses and explores the conversion role of HBeAg in different stages of chronic HBV infection.
- Hepatitis B， Chronic,
- Hepatitis B e Antigens,
- Immune Activation,
- Immune Suppressive

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【据Journal of Hepatology 2020年10月报道】题：肝细胞特异性NRF2激活可改善脂肪性肝炎的纤维化和癌变(作者Mohs A等)

慢性肝病中的炎症诱导氧化应激，因此可能导致肝损伤、纤维化和癌变的进展。KEAP1/NRF2轴是细胞氧化还原平衡的主要调节器。该研究探讨了KEAP1/NRF2系统是否参与了人类和小鼠肝病的进展。

在一个特征明确的非酒精性脂肪性肝病患者队列(n=63)中，通过肝RNA测序研究了氧化应激的临床相关性，并与组织学和临床参数进行相关分析。为了进行功能分析，将肝细胞特异性NEMO敲除(NEMO△hepa)小鼠与肝细胞特异性KEAP1敲除(KEAP1△hepa)小鼠杂交。

对人肝脏切片的免疫组织化学分析显示，慢性肝病患者的氧化应激增加，NRF2高表达。儿童非酒精性脂肪性肝病队列中肝脏样本的RNA测序显示，NRF2活化的显著增加与炎症分级相关，但与脂肪变性的分级无关，这在第二个成人非酒精性脂肪性肝病队列中得到证实。在小鼠中，微阵列分析显示KEAP1缺失诱导NRF2靶基因参与谷胱甘肽代谢和外源性应激(如Nqo1)。此外，在删除KEAP1后，NEMO△hepa肝脏中最重要的抗氧化剂之一谷胱甘肽(GSH)的缺乏得到了挽救。与NEMO△hepa肝相比，NEMO△hepa /KEAP1△hepa肝显示出细胞凋亡减少以及参与细胞周期调节和DNA复制的基因显著下调。因此，与NEMO△hepa相比，NEMO△hepa /KEAP1△hepa肝脏表现为纤维生成减少，肿瘤发生率降低，肿瘤数量减少，肿瘤大小减小。

非酒精性脂肪性肝炎患者的NRF2活化与炎症分级相关，但与脂肪变性无关。小鼠功能分析表明，在慢性肝病中，激活的NRF2通过改善纤维化、肝细胞癌变的发生和发展，而起到保护作用。

KEAP1/NRF2轴是细胞氧化还原平衡的主要调节系统。两个不同人群队列的非酒精性脂肪性肝炎患者中，NRF2的活性与炎症分级相关。在小鼠中，由于KEAP1缺失导致的NRF2激活可改善肝细胞的纤维化、肝细胞癌变的发生和进展。

摘译自MOHS A, OTTO T, SCHNEIDER KM, et al. Hepatocyte-specific NRF2 activation controls fibrogenesis and carcinogenesis in steatohepatitis[J]. J Hepatol, 2021, 74(3): 638-648.

(吉林大学第一医院感染病中心肝病科李丽华瑞报道)

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Role of HBeAg-induced immune activition and immunosuppression in chronic hepatitis B

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Role of HBeAg-induced immune activition and immunosuppression in chronic hepatitis B

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