mTOR complexes differentially orchestrates eosinophil development in allergy

Zhu, Chen; Xia, Lixia; Li, Fēi; Zhou, Lingren; Weng, Qingyu; Li, Zhouyang; Wu, Yangjie; Mao, Yuanyuan; Zhang, Chao; Wu, Yanping; Li, Miao; Ying, Songmin; Chen, Zhihua; Shen, Huahao; Li, Wen

doi:10.1038/s41598-018-25358-z

Cited by 17 publications

(17 citation statements)

References 51 publications

(86 reference statements)

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“…Furthermore, Zhu et al showed that mTOR inhibition suppress eosinophil differentiation in allergic airway inflammation [64], Shin and coll. that reduces eosinophil infiltration and Th2 immune response [65] and Fang et al that IgE induced airway smooth muscle cell (ASMC) remodeling was significantly reduced by inhibition of mTOR [66] while Rakhmanova et al suggested as a therapeutic strategy for mast cell-related diseases the hyperactivation of mTORC1 [67].…”

Section: Asthma and Rhinitismentioning

confidence: 99%

Sex and Gender Aspects for Patient Stratification in Allergy Prevention and Treatment

Martinis

Sirufo

Suppa

et al. 2020

IJMS

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Allergies are rapidly worsening in recent decades, representing the most common immunological diseases. The mechanism of disorders such as asthma, rhinocongiuntivitis, urticaria, atopic dermatitis, food and drug allergies, and anaphylaxis still remain unclear and consequently treatments is mostly still symptomatic and aspecific while developments of new therapies are limited. A growing amount of data in the literature shows us how the prevalence of allergic diseases is different in both sexes and its changes over the course of life. Genes, hormones, environmental and immunological factors affect sex disparities associated with the development and control of allergic diseases, while they more rarely are considered and reported regarding their differences related to social, psychological, cultural, economic, and employment aspects. This review describes the available knowledge on the role of sex and gender in allergies in an attempt to improve the indispensable gender perspective whose potential is still underestimated while it represents a significant turning point in research and the clinic. It will offer insights to stimulate exploration of the many aspects still unknown in this relationship that could ameliorate the preventive, diagnostic, and therapeutic strategies in allergic diseases.

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Section: Asthma and Rhinitismentioning

confidence: 99%

Sex and Gender Aspects for Patient Stratification in Allergy Prevention and Treatment

Martinis

Sirufo

Suppa

et al. 2020

IJMS

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“…Eosinophil extracellular trap formation has also been found to be correlated with autophagy levels (21,22), but interestingly Atg5 knockout was not necessary for their formation (82). Autophagy may have a role in the differentiation of eosinophils, however the only study of it has been through regulators, such as mTOR which regulates it indirectly (86,87). Like neutrophils, eosinophils have also been observed to go through an autophagy-mediated caspase-independent cell death in inflammatory conditions (88).…”

Section: Role Of Autophagy In Myeloid Cells Granulocytesmentioning

confidence: 99%

Role of Autophagy in Lung Inflammation

2020

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Autophagy is a cellular recycling system found in almost all types of eukaryotic organisms. The system is made up of a variety of proteins which function to deliver intracellular cargo to lysosomes for formation of autophagosomes in which the contents are degraded. The maintenance of cellular homeostasis is key in the survival and function of a variety of human cell populations. The interconnection between metabolism and autophagy is extensive, therefore it has a role in a variety of different cell functions. The disruption or dysfunction of autophagy in these cell types have been implicated in the development of a variety of inflammatory diseases including asthma. The role of autophagy in non-immune and immune cells both lead to the pathogenesis of lung inflammation. Autophagy in pulmonary non-immune cells leads to tissue remodeling which can develop into chronic asthma cases with long term effects. The role autophagy in the lymphoid and myeloid lineages in the pathology of asthma differ in their functions. Impaired autophagy in lymphoid populations have been shown, in general, to decrease inflammation in both asthma and inflammatory disease models. Many lymphoid cells rely on autophagy for effector function and maintained inflammation. In stark contrast, autophagy deficient antigen presenting cells have been shown to have an activated inflammasome. This is largely characterized by a T H 17 response that is accompanied with a much worse prognosis including granulocyte mediated inflammation and steroid resistance. The cell specificity associated with changes in autophagic flux complicates its targeting for amelioration of asthmatic symptoms. Differing asthmatic phenotypes between T H 2 and T H 17 mediated disease may require different autophagic modulations. Therefore, treatments call for a more cell specific and personalized approach when looking at chronic asthma cases. Viral-induced lung inflammation, such as that caused by SARS-CoV-2, also may involve autophagic modulation leading to inflammation mediated by lung resident cells. In this review, we will be discussing the role of autophagy in non-immune cells, myeloid cells, and lymphoid cells for their implications into lung inflammation and asthma. Finally, we will discuss autophagy's role viral pathogenesis, immunometabolism, and asthma with insights into autophagic modulators for amelioration of lung inflammation.

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“…This increase was partially related to an up-regulation of GATA1 with mTOR inhibition. Interestingly, mTOR deletion in myeloid cells promotes eosinophil development but disrupts neutrophil development [ 72 ].…”

Section: Role Of Mtor Signalling In Haemopoiesismentioning

confidence: 99%

The role of mTOR-mediated signals during haemopoiesis and lineage commitment

Malik

Sansom

Michie

2018

Biochemical Society Transactions

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The serine/threonine protein kinase mechanistic target of rapamycin (mTOR) has been implicated in the regulation of an array of cellular functions including protein and lipid synthesis, proliferation, cell size and survival. Here, we describe the role of mTOR during haemopoiesis within the context of mTORC1 and mTORC2, the distinct complexes in which it functions. The use of conditional transgenic mouse models specifically targeting individual mTOR signalling components, together with selective inhibitors, have generated a significant body of research emphasising the critical roles played by mTOR, and individual mTOR complexes, in haemopoietic lineage commitment and development. This review will describe the profound role of mTOR in embryogenesis and haemopoiesis, underscoring the importance of mTORC1 at the early stages of haemopoietic cell development, through modulation of stem cell potentiation and self-renewal, and erythroid and B cell lineage commitment. Furthermore, the relatively discrete role of mTORC2 in haemopoiesis will be explored during T cell development and B cell maturation. Collectively, this review aims to highlight the functional diversity of mTOR signalling and underline the importance of this pathway in haemopoiesis.

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mTOR complexes differentially orchestrates eosinophil development in allergy

Cited by 17 publications

References 51 publications

Sex and Gender Aspects for Patient Stratification in Allergy Prevention and Treatment

Sex and Gender Aspects for Patient Stratification in Allergy Prevention and Treatment

Role of Autophagy in Lung Inflammation

The role of mTOR-mediated signals during haemopoiesis and lineage commitment

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