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BATF Interference Blocks Th17 Cell Differentiation and Inflammatory Response in Hepatitis B Virus Transgenic Mice

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Abstract

Background

B cell-activating transcription factor (BATF) contributes to Th17 cell differentiation and pathological inflammatory responses.

Aims

This study explored BATF as a regulator of Th17 differentiation in normal and hepatitis B virus (HBV) transgenic mice.

Methods

Normal mice were divided into control, short hairpin RNA (shRNA) scramble, and shRNA BATF groups. HBV transgenic mice were divided into control, entecavir, shRNA scramble, entecavir + vector control, entecavir + shRNA scramble, shRNA BATF, and entecavir + shRNA BATF groups. Serum concentrations of AST, ALT, HBV-DNA, BATF, IL-17, and IL-22 and Th17 cell frequencies in the liver were compared among the groups. Correlations of serum HBV surface antigen (HBsAg), e-antigen (HBeAg), and core antigen (HBcAg) concentrations with BATF mRNA expression and the proportion of Th17 cells in the livers of HBV transgenic mice were also analyzed.

Results

Serum AST, ALT, BATF, IL-17, and IL-22 concentrations and Th17 cell proportions were higher in HBV transgenic mice relative to normal controls. Positive correlations of the HBcAg concentration with BATF mRNA and the proportion of Th17 cells were observed in HBV transgenic mice. BATF interference reduced the proportion of Th17 cells and serum IL-17 and IL-22 concentrations and led to obvious downregulation of AST, ALT, BATF, IL-17, and IL-22 expression and a reduced proportion of Th17 cells when combined with entecavir.

Conclusion

HBV markedly upregulated BATF expression and promoted Th17 cell activation. By contrast, BATF interference significantly impeded the proliferation of Th17 cells and secretion of IL-17 and IL-22 while alleviating hepatic lesions.

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Funding

This work was supported by the grants from National Natural Science Foundation of China (81171579, 81201287, 81300318, and 81371832), Key Project of Chinese Ministry of Science and Technology (2012ZX10002007 and 2013ZX10002001), and Science and Technology Development Plan of Shandong Province (2014GSF118068).

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Authors and Affiliations

  1. Department of Hepatology, Qilu Hospital of Shandong University, Jinan, 250012, China

    Long-Yan Chen, Xiao-Peng Fan, Yu-Chen Fan, Jing Zhao, Shuai Gao, Feng Li, Zhao-Xia Qi & Kai Wang

  2. Institute of Hepatology, Shandong University, Wenhuaxi Road 107#, Jinan, 250012, China

    Kai Wang

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  1. Long-Yan Chen
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  2. Xiao-Peng Fan
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  3. Yu-Chen Fan
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  4. Jing Zhao
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  6. Feng Li
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  7. Zhao-Xia Qi
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  8. Kai Wang
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Correspondence to Kai Wang.

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The authors declare that they have no conflict of interest.

Ethical approval

All mouse experiments were approved by the Institutional Animal Care and Use Committee (KYLL-2017(KS)-076).

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Chen, LY., Fan, XP., Fan, YC. et al. BATF Interference Blocks Th17 Cell Differentiation and Inflammatory Response in Hepatitis B Virus Transgenic Mice. Dig Dis Sci 64, 773–780 (2019). https://doi.org/10.1007/s10620-018-5392-x

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  • DOI: https://doi.org/10.1007/s10620-018-5392-x

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