IRF3 and IRF7 contribute to diesel exhaust particles‐induced pulmonary inflammation by mediating mTORC1 activation and restraining autophagy in mice,European Journal of Immunology

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IRF3 and IRF7 contribute to diesel exhaust particles‐induced pulmonary inflammation by mediating mTORC1 activation and restraining autophagy in mice
European Journal of Immunology ( IF 4.5 ) Pub Date : 2020-03-05 , DOI: 10.1002/eji.201948415
Yang Li ₁ , Chaoming Wang _{1,

2} , Xiangyu Wu ₃ , Hongbo Tian ₄ , Shanqun Jiang ₃ , Tao Xu ₁ , Zhiping Liu ₄ , Jin‐Lu Sun ₅ , Xiaopeng Qi _{1,

6}

Affiliation

Exposure to diesel exhaust particles (DEPs) is associated with acute inflammatory responses in the lung and exacerbation of respiratory diseases. However, the mechanism by which DEPs trigger the inflammatory responses remains unclear. Here, we demonstrated that the IFN response factors IRF3 and IRF7 played pivotal roles in DEP‐induced pulmonary inflammation. DEPs could not directly induce inflammatory cytokine expression in mouse cells, whereas DEPs triggered autophagy both in vitro and in vivo. The DEP‐induced autophagy was augmented in the absence of IRF3 and IRF7, but not in the absence of IFNAR. The expression of Raptor was induced by IRF3 and IRF7 in response to DEPs treatment. Furthermore, administration of the mechanistic target of rapamycin (mTOR) inhibitor alleviated the inflammatory responses in the lung during DEP exposure. Our findings define an IFNAR‐independent role of increased autophagy in the absence of IRF3 and IRF7 during pulmonary DEP exposure, and provide the basis to develop new therapeutic approaches to counteract the adverse effects of DEPs and possibly other ambient particulate matters.

中文翻译：

IRF3和IRF7通过介导mTORC1激活并抑制小鼠自噬来促进柴油机排气颗粒诱导的肺部炎症

暴露于柴油机排气颗粒（DEP）与肺部急性炎症反应和呼吸系统疾病加重有关。但是，DEPs触发炎症反应的机制仍不清楚。在这里，我们证明了IFN反应因子IRF3和IRF7在DEP诱导的肺部炎症中起关键作用。DEPs不能直接诱导小鼠细胞中炎性细胞因子的表达，而DEPs可以在体内和体外触发自噬。在没有IRF3和IRF7的情况下，DEP诱导的自噬会增强，而在没有IFNAR的情况下，则不会增强。猛禽的表情IRF3和IRF7对DEPs的治疗有诱导作用。此外，雷帕霉素（mTOR）抑制剂的机械目标的管理减轻了DEP暴露期间肺部的炎症反应。我们的发现定义了在肺DEP暴露期间缺乏IRF3和IRF7的情况下自噬增加的IFNAR依赖性作用，并为开发新的治疗方法以抵消DEP以及可能的其他环境颗粒物的不利影响提供了基础。

更新日期：2020-03-05

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