Rapamycin inhibition of eosinophil differentiation attenuates allergic airway inflammation in mice

Huang, Wen; Liu, Hui; Xia, Li-Xia; Tian, Bo; Huang, Huaqiong; Zhiyang, Chen; Ju, Zhenyu; Li, Wen; Chen, Zhihua; Shen, Huahao

doi:10.1111/resp.12554

Cited by 43 publications

(41 citation statements)

References 29 publications

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“…A number of stimulatory and inhibitory factors regulate these events, including interleukin (IL)‐5 . In a mouse model of allergic asthma, rapamycin was found to attenuate allergic airway inflammation through direct inhibition of eosinophil differentiation from eosinophil progenitor cells, which was independent of IL‐5 levels . As rapamycin can inhibit the mTOR pathway (a cell cycle regulatory pathway), the findings support the importance of this pathway in allergic airway disease.…”

Section: Asthmamentioning

confidence: 76%

Year in review 2015: Asthma and chronic obstructive pulmonary disease

et al. 2016

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Asthma continues to cause substantial morbidity and mortality, affecting some 300 million people worldwide, with a large proportion of those poorly controlled.1-3 In the last year, Respirology published a broad-based range of papers focusing on this important disease, ranging from questionnaire studies to molecular biology in mouse models. 4,5 This range of papers emphasizes the breadth of asthma research underway and the role of Respirology in disseminating these advances.

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Section: Asthmamentioning

confidence: 76%

Year in review 2015: Asthma and chronic obstructive pulmonary disease

et al. 2016

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“…Intriguingly, deletion of SGK1 in T cells makes mice resistant to experimentally induced asthma and enhances the TH1-dependant response to viral and tumor challenges. These positive effects of SGK1 inhibition could help to explain why some studies have found a positive effect of rapamycin on the immune system (Hua et al, 2015; Hurez et al, 2015). …”

Section: Mtor Signaling In the Aging Processmentioning

confidence: 91%

The Mechanistic Target of Rapamycin: The Grand ConducTOR of Metabolism and Aging

2016

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Summary Since the discovery that rapamycin, a small molecule inhibitor of the protein kinase mTOR (mechanistic Target Of Rapamycin), can extend the lifespan of model organisms including mice, interest in understanding the physiological role and molecular targets of this pathway has surged. While mTOR was already well known as a regulator of growth and protein translation, it is now clear that mTOR functions as a central coordinator of organismal metabolism in response to both environmental and hormonal signals. This review discusses recent developments in our understanding of how mTOR signaling is regulated by nutrients and the role of the mTOR signaling pathway in key metabolic tissues. Finally, we discuss the molecular basis for the negative metabolic side effects associated with rapamycin treatment, which may serve as barriers to the adoption of rapamycin or similar compounds for the treatment of diseases of aging and metabolism.

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“…Eosinophils are a tell-tale indicator of helminth infection, where they have been shown in certain settings to play host-protective roles. Despite their importance, little is known about the role of mTOR in their biology, other than the fact that rapamycin can inhibit the IL-5-dependent proliferation and differentiation of bone marrow precursors into eosinophils (Hua et al, 2015). …”

Section: Mtor In the Innate Immune Systemmentioning

confidence: 99%

MenTORing Immunity: mTOR Signaling in the Development and Function of Tissue-Resident Immune Cells

2017

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Tissue-resident immune cells must balance survival in peripheral tissues with the capacity to respond rapidly upon infection or tissue damage, and in turn couple these responses with intrinsic metabolic control and conditions in the tissue microenvironment. The serine/threonine kinase mammalian/mechanistic target of rapamycin (mTOR) is a central integrator of extracellular and intracellular growth signals and cellular metabolism and plays important roles in both innate and adaptive immune responses. This review discusses the function of mTOR signaling in the differentiation and function of tissue-resident immune cells, with focus on the role of mTOR as a metabolic sensor and its impact on metabolic regulation in innate and adaptive immune cells. We also discuss the impact of metabolic constraints in tissues on immune homeostasis and disease, and how manipulating mTOR activity with drugs such as rapamycin can modulate immunity in these contexts.

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Rapamycin inhibition of eosinophil differentiation attenuates allergic airway inflammation in mice

Cited by 43 publications

References 29 publications

Year in review 2015: Asthma and chronic obstructive pulmonary disease

Year in review 2015: Asthma and chronic obstructive pulmonary disease

The Mechanistic Target of Rapamycin: The Grand ConducTOR of Metabolism and Aging

MenTORing Immunity: mTOR Signaling in the Development and Function of Tissue-Resident Immune Cells

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