Background and objective: The mammalian target of rapamycin (mTOR) signalling pathway regulates immune responses, and promotes cell growth and differentiation. Inhibition of mTOR with rapamycin modulates allergic asthma, while the underlying molecular mechanisms remain elusive. Here, we demonstrate that rapamycin, effectively inhibits eosinophil differentiation, contributing to its overall protective role in allergic airway inflammation.

RationaleAcute lung injury (ALI) is a fatal but undertreated condition with severe neutrophilic inflammation, while little is known about the functions of eosinophils in pathogenesis of ALI.ObjectivesTo investigate the roles and molecular mechanisms of eosinophils in ALI.MethodsPulmonary eosinophils were identified by flow cytometry. Mice with abundant or deficient eosinophils were used. Cellularity of eosinophils and neutrophils in BALF, inflammatory assessment, and survival rate were detected. Human samples were also used for validating experimental results.ResultsBlood eosinophils were increased in survived individuals of patients with acute respiratory distress syndrome independent of the corticosteroid usage. There existed homeostatic eosinophils in lung parenchyma in mice, and these homeostatic eosinophils in originating from the bone marrow were predominantly CD101−. More CD101− eosinophils could be recruited earlier than lipopolysaccharide (LPS)-initiated neutrophilic inflammation. Loss of eosinophils augmented LPS-induced pulmonary injury. Homeostatic CD101− eosinophils ameliorated, while allergic CD101+ eosinophils exacerbated, the neutrophilic inflammation induced by LPS. Likewise, CD101 expression in eosinophils from ARDS patients did not differ from the healthy subjects. Mechanistically, CD101− eosinophils exhibited higher levels of Alox15 and Protectin D1. Administration of Protectin D1 isomer attenuated the neutrophilic inflammation.ConclusionsCollectively, our findings identify an uncovered function of native CD101− eosinophils in suppressing neutrophilic lung inflammation and suggest a potential therapeutic target for ALI.

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BackgroundAstragali radix Antiasthmatic Decoction (AAD), a traditional Chinese medication, is found effective in treating allergic diseases and chronic cough. The purpose of this study is to determine whether this medication could suppress allergen-induced airway hyperresponsiveness (AHR) and remodeling in mice, and its possible mechanisms.MethodsA mouse model of chronic asthma was used to investigate the effects of AAD on the airway lesions. Mice were sensitized and challenged with ovalbumin (OVA), and the extent of AHR and airway remodeling were characterized. Cells and cytokines in the bronchoalveolar lavage fluid (BALF) were examined.ResultsAAD treatment effectively decreased OVA-induced AHR, eosinophilic airway inflammation, and collagen deposition around the airway. It significantly reduced the levels of IL-13 and TGF-β1, but exerted inconsiderable effect on INF-γ and IL-10.ConclusionsAAD greatly improves the symptoms of allergic airway remodeling probably through inhibition of Th2 cytokines and TGF-β1.