期刊
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
卷 24, 期 11, 页码 6096-6106出版社
WILEY
DOI: 10.1111/jcmm.15202
关键词
B cell hyperactivation; chronic hepatitis B; NF-kappa B pathway; TLR4
资金
- Nanjing Medical Science and Technique Development Foundation [QRX17121]
- Jiangsu Science and Technology Development Plan [BE2017605]
- Medical Science and Technology Development Foundation of Nanjing [YKK16118]
- Natural Science Foundation of Jiangsu Province [BK20160121]
- National Natural Science Foundation of China [81672025, 81501749, 81600201, 81702011]
- Jiangsu Provincial Medical Innovation Team [CXTDA2017005]
- Foundation project of Jiangsu Commission of Health [Q2017003]
- Jiangsu Provincial Young Medical Talent [QNR2016007]
- Medical Science and technology development Foundation, Nanjing Department of Health [ZDX16004]
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-kappa B 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-kappa B 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.
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