mTOR complexes differentially orchestrates eosinophil development in allergy
Abstract Eosinophil infiltration is considered a hallmark in allergic airway inflammation, and the blockade of eosinophil differentiation may be an effective approach for treating eosinophil-related disorders. Mammalian target of rapamycin (mTOR) is a vital modulator in cell growth control and relat...
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| Format: | Article |
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Nature Portfolio
2018-05-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-018-25358-z |
| _version_ | 1818425348932501504 |
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| author | Chen Zhu Lixia Xia Fei Li Lingren Zhou Qingyu Weng Zhouyang Li Yinfang Wu Yuanyuan Mao Chao Zhang Yanping Wu Miao Li Songmin Ying Zhihua Chen Huahao Shen Wen Li |
| author_facet | Chen Zhu Lixia Xia Fei Li Lingren Zhou Qingyu Weng Zhouyang Li Yinfang Wu Yuanyuan Mao Chao Zhang Yanping Wu Miao Li Songmin Ying Zhihua Chen Huahao Shen Wen Li |
| author_sort | Chen Zhu |
| collection | DOAJ |
| description | Abstract Eosinophil infiltration is considered a hallmark in allergic airway inflammation, and the blockade of eosinophil differentiation may be an effective approach for treating eosinophil-related disorders. Mammalian target of rapamycin (mTOR) is a vital modulator in cell growth control and related diseases, and we have recently demonstrated that rapamycin can suppress eosinophil differentiation in allergic airway inflammation. Considering its critical role in haematopoiesis, we further investigated the role of mTOR in eosinophil differentiation in the context of asthmatic pathogenesis. Intriguingly, the inhibition of mTOR, either by genetic deletion or by another pharmacological inhibitor torin-1, accelerated the eosinophil development in the presence of IL-5. However, this was not observed to have any considerable effect on eosinophil apoptosis. The effect of mTOR in eosinophil differentiation was mediated by Erk signalling. Moreover, myeloid specific knockout of mTOR or Rheb further augmented allergic airway inflammation in mice after allergen exposure. Ablation of mTOR in myeloid cells also resulted in an increased number of eosinophil lineage-committed progenitors (Eops) in allergic mice. Collectively, our data uncovered the differential effects of mTOR in the regulation of eosinophil development, likely due to the distinct functions of mTOR complex 1 or 2, which thus exerts a pivotal implication in eosinophil-associated diseases. |
| first_indexed | 2024-12-14T14:12:31Z |
| format | Article |
| id | doaj.art-8bde9769a15a4d41966a45c2a91f6541 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-14T14:12:31Z |
| publishDate | 2018-05-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj.art-8bde9769a15a4d41966a45c2a91f65412022-12-21T22:58:17ZengNature PortfolioScientific Reports2045-23222018-05-018111410.1038/s41598-018-25358-zmTOR complexes differentially orchestrates eosinophil development in allergyChen Zhu0Lixia Xia1Fei Li2Lingren Zhou3Qingyu Weng4Zhouyang Li5Yinfang Wu6Yuanyuan Mao7Chao Zhang8Yanping Wu9Miao Li10Songmin Ying11Zhihua Chen12Huahao Shen13Wen Li14Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital, Zhejiang University School of MedicineDepartment of Respiratory and Critical Care Medicine, The Second Affiliated Hospital, Zhejiang University School of MedicineDepartment of Respiratory and Critical Care Medicine, The Second Affiliated Hospital, Zhejiang University School of MedicineDepartment of Respiratory and Critical Care Medicine, The Second Affiliated Hospital, Zhejiang University School of MedicineDepartment of Respiratory and Critical Care Medicine, The Second Affiliated Hospital, Zhejiang University School of MedicineDepartment of Respiratory and Critical Care Medicine, The Second Affiliated Hospital, Zhejiang University School of MedicineDepartment of Respiratory and Critical Care Medicine, The Second Affiliated Hospital, Zhejiang University School of MedicineDepartment of Respiratory Medicine, Ningbo No. 2 HospitalDepartment of Respiratory and Critical Care Medicine, The Second Affiliated Hospital, Zhejiang University School of MedicineDepartment of Respiratory and Critical Care Medicine, The Second Affiliated Hospital, Zhejiang University School of MedicineDepartment of Respiratory and Critical Care Medicine, The Second Affiliated Hospital, Zhejiang University School of MedicineDepartment of Respiratory and Critical Care Medicine, The Second Affiliated Hospital, Zhejiang University School of MedicineDepartment of Respiratory and Critical Care Medicine, The Second Affiliated Hospital, Zhejiang University School of MedicineDepartment of Respiratory and Critical Care Medicine, The Second Affiliated Hospital, Zhejiang University School of MedicineDepartment of Respiratory and Critical Care Medicine, The Second Affiliated Hospital, Zhejiang University School of MedicineAbstract Eosinophil infiltration is considered a hallmark in allergic airway inflammation, and the blockade of eosinophil differentiation may be an effective approach for treating eosinophil-related disorders. Mammalian target of rapamycin (mTOR) is a vital modulator in cell growth control and related diseases, and we have recently demonstrated that rapamycin can suppress eosinophil differentiation in allergic airway inflammation. Considering its critical role in haematopoiesis, we further investigated the role of mTOR in eosinophil differentiation in the context of asthmatic pathogenesis. Intriguingly, the inhibition of mTOR, either by genetic deletion or by another pharmacological inhibitor torin-1, accelerated the eosinophil development in the presence of IL-5. However, this was not observed to have any considerable effect on eosinophil apoptosis. The effect of mTOR in eosinophil differentiation was mediated by Erk signalling. Moreover, myeloid specific knockout of mTOR or Rheb further augmented allergic airway inflammation in mice after allergen exposure. Ablation of mTOR in myeloid cells also resulted in an increased number of eosinophil lineage-committed progenitors (Eops) in allergic mice. Collectively, our data uncovered the differential effects of mTOR in the regulation of eosinophil development, likely due to the distinct functions of mTOR complex 1 or 2, which thus exerts a pivotal implication in eosinophil-associated diseases.https://doi.org/10.1038/s41598-018-25358-z |
| spellingShingle | Chen Zhu Lixia Xia Fei Li Lingren Zhou Qingyu Weng Zhouyang Li Yinfang Wu Yuanyuan Mao Chao Zhang Yanping Wu Miao Li Songmin Ying Zhihua Chen Huahao Shen Wen Li mTOR complexes differentially orchestrates eosinophil development in allergy Scientific Reports |
| title | mTOR complexes differentially orchestrates eosinophil development in allergy |
| title_full | mTOR complexes differentially orchestrates eosinophil development in allergy |
| title_fullStr | mTOR complexes differentially orchestrates eosinophil development in allergy |
| title_full_unstemmed | mTOR complexes differentially orchestrates eosinophil development in allergy |
| title_short | mTOR complexes differentially orchestrates eosinophil development in allergy |
| title_sort | mtor complexes differentially orchestrates eosinophil development in allergy |
| url | https://doi.org/10.1038/s41598-018-25358-z |
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