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TAOK1 negatively regulates IL-17-mediated signaling and inflammation

Cellular & Molecular Immunology volume 15, pages 794–802 (2018)Cite this article

A Correction to this article was published on 29 May 2018

Abstract

Interleukin 17 (IL-17) is an important cytokine that can induce tissue inflammation and is involved in the pathogenesis of numerous autoimmune diseases. However, the regulation of its signaling transduction has not been well described. In this study, we report that thousand and one kinase 1 (TAOK1) functions as a negative regulator of IL-17-mediated signal transduction and inflammation. TAOK1 knockdown promotes IL-17-induced cytokine and chemokine expression and the activation of mitogen-activated protein kinases and nuclear factor-κB. We further demonstrate that TAOK1 interacts with IL-17 receptor A (IL-17RA) independent of its kinase activity, and TAOK1 dose-dependently prevents the formation of the IL-17R-Act1 (nuclear factor activator 1, also known as tumor necrosis factor receptor-associated factor 3 interacting protein 2) complex. Consistent with this, TAOK1 deficiency exacerbates colitis in the 2,4,6-trinitrobenzenesulfonic acid)-induced experimental model of inflammatory bowel disease, likely by its promotion of the IL-17-mediated signaling pathway. TAOK1 expression is decreased in the colons of ulcerative colitis patients. In conclusion, these findings suggest that TAOK1 is involved in the development of IL-17-related autoimmune disorders.

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Acknowledgements

This work was supported by grants from the National Key Research and Development Program of China (2016YFA0502201), the National Natural Science Foundation of China (81571550, 81671613), the Natural Science Foundation of Zhejiang Province (LY18H100001, LY15H100001), the ‘Double First-rate’ project initiatives, the Shanghai Key Laboratory of Cell Engineering (14DZ2272300) and the Shanghai Leading Academic Discipline Project (B905).

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  1. These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Cell Biology, School of Basic Medical Sciences, Zhejiang University, Hangzhou, 310058, China

    Zhaoru Zhang & Jun Zhou

  2. Cancer Institute, Institute of Translational Medicine, Second Military Medical University, Shanghai, 200433, China

    Zhen Tang & Huazhang An

  3. Scientific Research Center, Shanghai Public Health Clinical Center, Fudan University, Shanghai, 201508, China

    Xianwei Ma

  4. The Second Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, 310005, China

    Kai Sun & Liping Fan

  5. Department of Clinical Medicine, Zhejiang University City College School of Medicine, Hangzhou, 310015, China

    Jie Fang & Jianping Pan

  6. Institute of Immunology, School of Medicine, Zhejiang University, Hangzhou, 310058, China

    Xiaojian Wang

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  1. Zhaoru Zhang
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Zhang, Z., Tang, Z., Ma, X. et al. TAOK1 negatively regulates IL-17-mediated signaling and inflammation. Cell Mol Immunol 15, 794–802 (2018). https://doi.org/10.1038/cmi.2017.158

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