慢性乙型肝炎患者通过TLR4引起的乙型肝炎病毒诱导的B细胞过

StephenW

J Cell Mol Med. 2020 May 11. doi: 10.1111/jcmm.15202. [Epub ahead of print]
Hepatitis B virus-induced hyperactivation of B cells in chronic hepatitis B patients via TLR4.
Li Y1, Yin S1, Chen Y2, Zhang Q3, Huang R1, Jia B1, Jie W1, Yao K1, Wang J1, Tong X1, Liu Y3, Wu C1.
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Abstract

B cell hyperactivation and functional impairment were identified from patients with chronic hepatitis B virus (CHB) infection; however, the underlying mechanism remains unknown. Here, we aim to elucidate the mechanisms responsible for B cell hyperactivation during HBV infection. Peripheral CD19+  B cells isolated from 4 CHB patients and 4 healthy volunteers were analysed by RNA sequencing. A total of 1401 differentially expressed genes were identified from B cell transcriptome of CHB patients vs healthy volunteers. We found that B cells from CHB patients were functional impaired, with increased TLR4 expression, activated NF-κB pathway and altered mitochondrial function. The expression of B cell activation-related genes, including TLR4, was further validated using additional clinical samples. To further verify the role of TLR4 in B cell activation during CHB, B cell phenotypes were determined in wild-type (WT) and TLR4-/- HBV-carrier mice. Hyperactivated B cell and TLR4 signalling pathway were observed in WT HBV-carrier mice, while TLR4 ablation failed to induce B cell hyperactivation, and downstream MyD88 and NF-κB were also not altered. Taken together, TLR4 pathway plays a pivotal role in B cell hyperactivation during CHB, which might serve as a promising target for B cell function restoration.

© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.
KEYWORDS:

B cell hyperactivation; NF-κB pathway; TLR4; chronic hepatitis B

PMID:
    32391647
DOI:
    10.1111/jcmm.15202

StephenW

J细胞分子医学。 2020年5月11日。doi：10.1111 / jcmm.15202。 [Epub提前发布]
慢性乙型肝炎患者通过TLR4引起的乙型肝炎病毒诱导的B细胞过度活化。
李Y1，尹S1，陈Y2，张Q3，黄R1，贾B1，杰W1，姚K1，王J1，童X1，刘Y3，吴C1。
作者信息
抽象

从慢性乙型肝炎病毒（CHB）感染患者中鉴定出B细胞过度活化和功能受损；但是，其潜在机制仍然未知。在这里，我们旨在阐明造成HBV感染期间B细胞过度活化的机制。通过RNA测序分析了从4位CHB患者和4位健康志愿者中分离出的外周CD19 + B细胞。从CHB患者与健康志愿者的B细胞转录组中鉴定出总共1401个差异表达基因。我们发现来自CHB患者的B细胞功能受损，TLR4表达增加，NF-κB通路激活，线粒体功能改变。使用其他临床样品进一步验证了B细胞活化相关基因（包括TLR4）的表达。为了进一步验证TLR4在CHB期间B细胞活化中的作用，在野生型（WT）和TLR4-/-HBV携带者小鼠中确定了B细胞表型。在野生型HBV携带者小鼠中观察到B细胞和TLR4信号通路过度活化，而TLR4消融未能诱导B细胞过度活化，下游MyD88和NF-κB也未改变。两者合计，TLR4通路在慢性乙型肝炎期间B细胞过度激活中起着关键作用，这可能是B细胞功能恢复的有希望的目标。

©2020作者。细胞与分子医学基金会和约翰·威利父子有限公司出版的《细胞与分子医学杂志》。
关键字：

B细胞过度活化； NF-κB途径； TLR4；慢性乙型肝炎

PMID：
    32391647
DOI：
    10.1111 / jcmm.15202

StephenW

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/jcmm.15202