Activation of the mTOR signaling pathway is required for asthma onset

The mTOR pathway has been implicated in immune functions; however, its role in asthma is not well understood. We found that patients experiencing an asthma attack, when compared with patients in asthma remission, showed significantly elevated serum mTOR pathway activation, increased Th17 cells and I...

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Bibliographic Details
Published in:	Scientific reports 2017-07, Vol.7 (1), p.4532-13, Article 4532
Main Authors:	Zhang, Yanli, Jing, Ying, Qiao, Junying, Luan, Bin, Wang, Xiufang, Wang, Li, Song, Zhe
Format:	Article
Language:	eng
Subjects:	1-Phosphatidylinositol 3-kinase AKT protein Animals Asthma Asthma - drug therapy Asthma - etiology Asthma - metabolism Asthma - pathology Biomarkers Child Child, Preschool Cytokines - metabolism Disease Models, Animal Female Helper cells Humans Interferon Interleukin 4 Lymphocytes T Male Mice Ovalbumin Protein Kinase Inhibitors - pharmacology Remission Signal transduction Signal Transduction - drug effects T-Lymphocyte Subsets - immunology T-Lymphocyte Subsets - metabolism Th1 Cells - drug effects Th1 Cells - immunology Th1 Cells - metabolism Th17 Cells - drug effects Th17 Cells - immunology Th17 Cells - metabolism Th2 Cells - drug effects Th2 Cells - immunology Th2 Cells - metabolism TOR protein TOR Serine-Threonine Kinases - metabolism γ-Interferon
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Summary:	The mTOR pathway has been implicated in immune functions; however, its role in asthma is not well understood. We found that patients experiencing an asthma attack, when compared with patients in asthma remission, showed significantly elevated serum mTOR pathway activation, increased Th17 cells and IL-4, and decreased Treg cells and IFN-γ. In patients experiencing asthma, mTOR activation was positively correlated with the loss of Th17/Treg and Th1/Th2 balance. The role of mTOR in asthma was further confirmed using an ovalbumin-induced asthmatic mouse model. The mTOR pathway was activated in asthmatic mice, demonstrated by elevated levels of p-PI3K, p-Akt, p-mTOR, and p-p70S6k, and this activation was significantly reduced by treatment with budenoside or mTOR pathway inhibitors. Moreover, mTOR pathway inhibitor treatment reduced asthmatic markers and reversed the Th17/Treg and Th1/Th2 imbalances in asthmatic mice. Finally, different mTOR pathway inhibitor treatments have different inhibitory effects on signaling molecules in asthmatic mice. In summary, mTOR is activated during asthma onset and suppressed during asthma remission, and inhibiting the mTOR pathway in asthmatic mice alleviates asthmatic markers and restores the balances of Th17/Treg and Th1/Th2 cytokines. These data strongly suggest a critical requirement for mTOR pathway activation in asthma onset, suggesting potential targets for asthma treatments.
ISSN:	2045-2322 2045-2322