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CD8+ T cell/IL-33/ILC2 axis exacerbates the liver injury in Con A-induced hepatitis in T cell-transferred Rag2-deficient mice

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Abstract

Background

Previous studies showed that CD4+ T cells play a critical role in Con A-induced hepatitis in wild-type mice. However, the role of CD8+ T cells in the setting of Con A-induced hepatitis is enigmatic. The aim of study is to investigate the function of CD8+ T cells in the context of Con-A-induced hepatitis.

Materials and subjects

Two different mouse models of Con A-induced hepatitis, T cell-transferred Rag2−/− mice and wild-type C57BL/6 mice, were used in the present study. IL-33 gene knockout mice were used to confirm the role of alarmin in Con A-induced hepatitis.

Results

Opposing to the previous results obtained in wild-type mice, transferred CD4+ T cells alone into Rag2-knockout mice cannot cause hepatitis upon Con A challenge. In stark contrast, transferred CD8+ T cells play an important role in the pathogenesis of Con A-induced liver injury in T cell-transferred Rag2-deficient mice. Furthermore, we found that hepatocytes injured by perforin-based CD8+ T cell cytotoxicity release the alarmin IL-33. This cytokine promotes ST2+ ILC2 development and the secretion of cytokines IL-5 and IL-13 to mediate liver inflammation triggered by Con A challenge. In addition, these type 2 cytokines, including those originated from CD4+ T cells, result in eosinophils accumulation in liver to exacerbate the liver injury after Con A administration.

Conclusion

Our data for the first time revealed that CD8+ T cells play an indispensable role in the pathogenesis of Con A-induced liver injury in T cell-transferred Rag2-deficient mice. Therefore, the CD8+ T cell/IL-33/ILC2 axis is a potential therapeutic target for acute immune-mediated liver injury.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (91542110, 81373167 to M. Fang). We thank Mr. Yong Xu and Zhihui Liang for technical assistance with flow cytometry.

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Authors and Affiliations

  1. Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, 13# Hangkong Road, Wuhan, 430030, China

    Yuanyue Zhang, Chang Qi, Lingyun Li, Shuyao Hua, Fang Zheng, Feili Gong & Min Fang

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  1. Yuanyue Zhang
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  2. Chang Qi
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  3. Lingyun Li
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  4. Shuyao Hua
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  7. Min Fang
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Contributions

YZ and CQ performed the experiments. LL and SH analyzed the data. FZ and FG provided the animal model and suggestions in experimental design. YZ and MF designed the experiments, analyzed data and wrote the paper.

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Correspondence to Min Fang.

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The authors report no conflict of interest.

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Responsible Editor: Mauro Teixeira.

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Zhang, Y., Qi, C., Li, L. et al. CD8+ T cell/IL-33/ILC2 axis exacerbates the liver injury in Con A-induced hepatitis in T cell-transferred Rag2-deficient mice. Inflamm. Res. 68, 75–91 (2019). https://doi.org/10.1007/s00011-018-1197-9

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  • DOI: https://doi.org/10.1007/s00011-018-1197-9

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