mTOR complexes differentially orchestrates eosinophil development in allergy

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 diseas...

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Published in:Scientific reports 2018-05, Vol.8 (1), p.6883-14, Article 6883
Main Authors: Zhu, Chen, Xia, Lixia, Li, Fei, Zhou, Lingren, Weng, Qingyu, Li, Zhouyang, Wu, Yinfang, Mao, Yuanyuan, Zhang, Chao, Wu, Yanping, Li, Miao, Ying, Songmin, Chen, Zhihua, Shen, Huahao, Li, Wen
Format: Article
Language:English
Subjects:
13/1
13/100
13/106
13/31
38/77
64/60
692/4017
692/699/1785/31
82/80
96/21
Allergens
Allergies
Apoptosis
Asthma
Clonal deletion
Humanities and Social Sciences
Inflammation
Interleukin 5
Leukocytes (eosinophilic)
multidisciplinary
Myeloid cells
Rapamycin
Respiratory tract
Respiratory tract diseases
Science
Science (multidisciplinary)
TOR protein
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Summary: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.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-018-25358-z