IL-17A-producing T cells exacerbate fine particulate matter-induced lung inflammation and fibrosis by inhibiting PI3K/Akt/mTOR-mediated autophagy
IL-17A-producing T cells exacerbate fine particulate matter-induced lung inflammation and fibrosis by inhibiting PI3K/Akt/mTOR-mediated autophagy
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DOI：
10.1111/jcmm.15475
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发表时间：
2020-07-09
影响因子：
5.3
通讯作者：
Duan, Jun
中科院分区：
文献类型：
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作者：
Cong, Lu-Hong;Li, Tao;Duan, Jun
细颗粒物（PM2.5）是能够引起气道损伤的主要空气污染物。令人信服的证据表明IL-17 A参与肺损伤，而其对PM2.5诱导的肺损伤的贡献在很大程度上仍然未知。本文探讨了IL-17 A在PM2.5诱导的小鼠肺损伤模型中的可能作用。小鼠灌胃PM2.5建立肺损伤模型。进行流式细胞术以分离γ δ T和Th 17细胞。ELISA法检测灌洗液上清液中炎性因子的表达。提取原代支气管上皮细胞（mBECs），采用免疫荧光法和Western blot法检测mBECs中TGF信号通路、自噬信号通路和PI 3 K/Akt/mTOR信号通路相关蛋白的表达。并对线粒体功能进行了评价。PM2.5通过增强γ δ T/Th 17细胞分泌IL-17 A而加重炎症反应。同时，PM2.5激活TGF信号通路，诱导支气管上皮细胞的EMT进展，从而促进肺纤维化。此外，PM2.5通过上调IL-17 A抑制支气管上皮细胞自噬，进而激活PI 3 K/Akt/mTOR信号通路。此外，IL-17 A损害了PM2.5诱导模型中气道上皮细胞的能量代谢。本研究提示，PM2.5可通过诱导γ δ T和Th 17细胞分泌IL-17 A，调节PI 3 K/Akt/mTOR信号通路，抑制支气管上皮细胞自噬，促进肺部炎症和纤维化。
Fine particulate matter (PM2.5) is the primary air pollutant that is able to induce airway injury. Compelling evidence has shown the involvement of IL-17A in lung injury, while its contribution to PM2.5-induced lung injury remains largely unknown. Here, we probed into the possible role of IL-17A in mouse models of PM2.5-induced lung injury. Mice were instilled with PM2.5 to construct a lung injury model. Flow cytometry was carried out to isolate gamma delta T and Th17 cells. ELISA was adopted to detect the expression of inflammatory factors in the supernatant of lavage fluid. Primary bronchial epithelial cells (mBECs) were extracted, and the expression of TGF signalling pathway-, autophagy- and PI3K/Akt/mTOR signalling pathway-related proteins in mBECs was detected by immunofluorescence assay and Western blot analysis. The mitochondrial function was also evaluated. PM2.5 aggravated the inflammatory response through enhancing the secretion of IL-17A by gamma delta T/Th17 cells. Meanwhile, PM2.5 activated the TGF signalling pathway and induced EMT progression in bronchial epithelial cells, thereby contributing to pulmonary fibrosis. Besides, PM2.5 suppressed autophagy of bronchial epithelial cells by up-regulating IL-17A, which in turn activated the PI3K/Akt/mTOR signalling pathway. Furthermore, IL-17A impaired the energy metabolism of airway epithelial cells in the PM2.5-induced models. This study suggested that PM2.5 could inhibit autophagy of bronchial epithelial cells and promote pulmonary inflammation and fibrosis by inducing the secretion of IL-17A in gamma delta T and Th17 cells and regulating the PI3K/Akt/mTOR signalling pathway.