IL‐17A‐producing T cells exacerbate fine particulate matter‐induced lung inflammation and fibrosis by inhibiting PI3K/Akt/mTOR‐mediated autophagy

• Published in: Journal of cellular and molecular medicine 2020-08, Vol.24 (15), p.8532-8544
• Main Authors: Cong, Lu‐Hong, Li, Tao, Wang, Hui, Wu, Yi‐Na, Wang, Shu‐Peng, Zhao, Yu‐Yue, Zhang, Guo‐Qiang, Duan, Jun
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; Adenoviruses; AKT protein; Alcohol; Animal models; Animals; Asthma; Autophagy; Cells, Cultured; Chronic obstructive pulmonary disease; Cytokines; Dehydrogenases; Disease; Disease Models, Animal; Disease Susceptibility; Energy metabolism; Enzyme-linked immunosorbent assay; Epithelial Cells; Fibrosis; Flow cytometry; Growth factors; Helper cells; Humans; IL‐17A; Immunofluorescence; Inflammation; Interleukin-17 - biosynthesis; Kinases; Laboratory animals; Lung diseases; lung injury; Lymphocytes T; Male; Mice; Mitochondria; Mortality; Original; Outdoor air quality; Particulate matter; Particulate Matter - adverse effects; Phagocytosis; Phosphatidylinositol 3-Kinases - metabolism; PI3K/Akt/mTOR signalling pathway; PM2.5; Pneumonia - etiology; Pneumonia - metabolism; Pneumonia - pathology; Pollutants; Polymerase chain reaction; Proteins; Proto-Oncogene Proteins c-akt - metabolism; Pulmonary fibrosis; Pulmonary Fibrosis - etiology; Pulmonary Fibrosis - metabolism; Pulmonary Fibrosis - pathology; pulmonary inflammatory response; Receptors, Antigen, T-Cell, gamma-delta - metabolism; Respiratory tract; Signal Transduction; T Cell Transcription Factor 1 - immunology; T Cell Transcription Factor 1 - metabolism; Th17 Cells - immunology; Th17 Cells - metabolism; TOR protein; TOR Serine-Threonine Kinases - metabolism; Transforming Growth Factor beta - metabolism; Tumor necrosis factor-TNF
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/jcmm.15475

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 γδT 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 γδT/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 γδT and Th17 cells and regulating the PI3K/Akt/mTOR signalling pathway.