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Eosinophilic Bronchitis, Eosinophilia Associated Genetic Variants, and Notch Signaling in Asthma

机译:嗜酸性支气管炎,嗜酸性粒细胞相关遗传变异和哮喘中的Notch信号

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While much has indeed been learned about the biology and role of eosinophils, the paradigm of eosinophils has the pros and cons in development of asthma. To answer the questions in the black box, this review firstly discusses the biological and morphological differences between asthma and eosinophilic bronchitis (EB). EB is an interesting clinical manifestation of eosinophilic airway disease that does not involve airway hyperresponsiveness (AHR), demonstrating that airway eosinophilia alone is insufficient to merit a diagnosis of asthma. Secondly, I will describe and discuss the effect(s) of single-nucleotide polymorphisms (SNPs) in the genes CCR3 , IL-5 RECEPTOR ALPHA (IL5RA) , and IL1RL1 , and finally the in vitro and in vivo effects of Notch inhibition on both eosinophil differentiation and experimental asthma. Eosinophilic airway inflammation is not as important in the pathogenesis and maintenance of asthma as had previously been thought. However, the role of eosinophils in other asthma subphenotypes, including refractory or severely remodeled asthma, needs to be evaluated further. High-throughput methodologies such as genomics will facilitate the discovery of new markers of inflammation; these, in turn, will aid in the evaluation of the role of eosinophils in asthma and its various subphenotypes.
机译:尽管确实已经了解了很多关于嗜酸性粒细胞的生物学和作用的信息,但嗜酸性粒细胞的范例在哮喘的发展中具有优缺点。为了回答黑匣子中的问题,本文首先讨论哮喘与嗜酸性支气管炎(EB)之间的生物学和形态学差异。 EB是嗜酸性气道疾病的有趣临床表现,不涉及气道高反应性(AHR),表明仅气道嗜酸性粒细胞不足不足以诊断为哮喘。其次,我将描述和讨论单核苷酸多态性(SNP)在CCR3,IL-5受体ALPHA(IL5RA)和IL1RL1基因中的作用,最后讨论Notch抑制在体内和体外的作用。嗜酸性粒细胞分化和实验性哮喘。嗜酸性气道炎症在哮喘的发病机理和维持中并不像以前所认为的那么重要。但是,嗜酸性粒细胞在其他哮喘亚表型中的作用,包括难治性或重度哮喘,需要进一步评估。基因组学等高通量方法学将有助于发现炎症的新标记;这些反过来将有助于评估嗜酸性粒细胞在哮喘及其各种亚表型中的作用。

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