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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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8bde9769a15a4d41966a45c2a91f6541
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spelling	oai:doaj.org-article:8bde9769a15a4d41966a45c2a91f65412021-12-02T12:32:35ZmTOR complexes differentially orchestrates eosinophil development in allergy10.1038/s41598-018-25358-z2045-2322https://doaj.org/article/8bde9769a15a4d41966a45c2a91f65412018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25358-zhttps://doaj.org/toc/2045-2322Abstract 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.Chen ZhuLixia XiaFei LiLingren ZhouQingyu WengZhouyang LiYinfang WuYuanyuan MaoChao ZhangYanping WuMiao LiSongmin YingZhihua ChenHuahao ShenWen LiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-14 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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
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.
format	article
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
title	mTOR complexes differentially orchestrates eosinophil development in allergy
title_short	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_sort	mtor complexes differentially orchestrates eosinophil development in allergy
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/8bde9769a15a4d41966a45c2a91f6541
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_version_	1718394047008079872

mTOR complexes differentially orchestrates eosinophil development in allergy

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