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Blockade of IL-33 ameliorates Con A-induced hepatic injury by reducing NKT cell activation and IFN-γ production in mice

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Abstract

IL-33, a recently described member of the IL-1 family, has been identified as a cytokine endowed with pro-Th2 type functions. To date, there are only limited data on its role in physiological and pathological hepatic immune responses. In this study, we examined the role of IL-33 in immune-mediated liver injury by exploring the model of concanavalin A (Con A)-induced hepatitis. We observed that the level of IL-33 expression in the liver was dramatically increased at 12 h after Con A injection. Meanwhile, ST2L, the receptor of IL-33, was significantly up-regulated in lymphocytes including T and natural killer T (NKT) cells, especially in NKT cells. Moreover, administration of recombinant IL-33 exacerbated Con A-induced hepatitis, while pretreatment of IL-33-blocking antibody or psST2-Fc plasmids showed a protective effect probably by inhibiting the activation of late stage of T cells and NKT cells and also decreasing the production of the cytokine IFN-γ. Furthermore, depletion of NKT cells abolished the protective effect of IL-33-blocking antibody, and IL-33 failed to exacerbate Con A-induced hepatitis in IFN-γ−/− mice. These data suggested the critical roles of NKT cells and IFN-γ in the involvement of IL-33 in Con A-induced hepatitis. Blockade of IL-33 may represent a novel therapeutic strategy through IL-33/ST2L signal to prevent immune-mediated liver injury.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (grant 81072440) and the Ministry of Science and Technology of China (grant 2007CB512402).

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The authors declare no conflict of interests related to this study.

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Authors and Affiliations

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

    Jie Chen, Lihua Duan, Ali Xiong, Hongwei Zhang, Fang Zheng, Zheng Tan, Feili Gong & Min Fang

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  1. Jie Chen
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  2. Lihua Duan
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  3. Ali Xiong
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  4. Hongwei Zhang
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  7. Feili Gong
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  8. Min Fang
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Correspondence to Feili Gong or Min Fang.

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Chen, J., Duan, L., Xiong, A. et al. Blockade of IL-33 ameliorates Con A-induced hepatic injury by reducing NKT cell activation and IFN-γ production in mice. J Mol Med 90, 1505–1515 (2012). https://doi.org/10.1007/s00109-012-0938-4

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  • DOI: https://doi.org/10.1007/s00109-012-0938-4

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