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Inflammation Research

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14.11.2018 | Original Research Paper

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

verfasst von: Yuanyue Zhang, Chang Qi, Lingyun Li, Shuyao Hua, Fang Zheng, Feili Gong, Min Fang

Erschienen in: Inflammation Research | Ausgabe 1/2019

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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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Titel: CD8+ T cell/IL-33/ILC2 axis exacerbates the liver injury in Con A-induced hepatitis in T cell-transferred Rag2-deficient mice
verfasst von: Yuanyue Zhang
Chang Qi
Lingyun Li
Shuyao Hua
Fang Zheng
Feili Gong
Min Fang
Publikationsdatum: 14.11.2018
Verlag: Springer International Publishing
Erschienen in: Inflammation Research / Ausgabe 1/2019
Print ISSN: 1023-3830
Elektronische ISSN: 1420-908X
DOI: https://doi.org/10.1007/s00011-018-1197-9

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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

Abstract

Background

Materials and subjects

Results

Conclusion

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Abstract

Background

Materials and subjects

Results

Conclusion

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