TAOK1 negatively regulates IL-17-mediated signaling and inflammation
TAOK1 negatively regulates IL-17-mediated signaling and inflammation
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DOI：
10.1038/cmi.2017.158
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发表时间：
2018-02
影响因子：
24.1
通讯作者：
Zhaoru Zhang;Zhen Tang;Xianwei Ma;K. Sun;L. Fan;Jie Fang;Jianping Pan;Xiaojian Wang;
中科院分区：
文献类型：
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作者：
Zhaoru Zhang;Zhen Tang;Xianwei Ma;K. Sun;L. Fan;Jie Fang;Jianping Pan;Xiaojian Wang;
白细胞介素17（IL-17）是一种重要的细胞因子，可诱导组织炎症，并参与许多自身免疫性疾病的发病机制。然而，其信号转导的调节还没有得到很好的描述。在这项研究中，我们报告，一千零一激酶1（TAOK 1）的功能作为一个负调节IL-17介导的信号转导和炎症。TAOK 1敲低促进IL-17诱导的细胞因子和趋化因子表达以及促分裂原活化蛋白激酶和核因子-κB的活化。我们进一步证明，TAOK 1与IL-17受体A（IL-17 RA）相互作用独立于其激酶活性，TAOK 1剂量依赖性地阻止IL-17 R-Act 1（核因子激活因子1，也称为肿瘤坏死因子受体相关因子3相互作用蛋白2）复合物的形成。与此一致，TAOK 1缺乏在2，4，6-三硝基苯磺酸诱导的炎性肠病实验模型中加重结肠炎，可能是通过其促进IL-17介导的信号传导途径。TAOK 1在溃疡性结肠炎患者结肠中的表达降低。总之，这些发现表明TAOK 1参与了IL-17相关的自身免疫性疾病的发展。
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.