摘要
背景:白细胞介素(IL)- 17在众多的免疫和炎症反应中起着至关重要的作用,最近被认为在非特应性(非嗜酸性粒细胞/中性粒细胞主导的)哮喘的发病机制中起到很大作用。我们旨在比较在变应性和非变应性哮喘中、有无使用吸入性皮质类固醇(ICS)对支气管气道中IL-17表达的影响,并识别其主要细胞来源。
方法:对114例轻中度哮喘患者的支气管活检进行了研究:33例非特应性,63例非类固醇使用者,90例不吸烟者。若将吸入性皮质类固醇使用者和吸烟者考虑进去,IL-17的表达与过敏和炎症细胞计数相关(EPX, NP57, CD3, CD4, CD8, CD20, CD68)。使用多元线性回归分析来确定独立因素以及最相关的促进IL-17表达的炎症细胞。双重免疫染色实验被用来证实IL-17的主要细胞来源。
结果:在不使用吸入性皮质类固醇激素的病例中,非过敏性哮喘比过敏性哮喘在气道壁有更多的IL-17+细胞。在过敏性和非过敏性哮喘中,吸入性皮质类固醇激素的使用与较低数量的IL-17+细胞相关,与是否吸烟无关。IL-17+细胞数和中性粒细胞数(B:0.26,95%CI:0.17-0.35)以及嗜酸性粒细胞数相关(B:0.18,95%CI:0.07-0.29)。经双重免疫染色实验证实IL-17+细胞主要为中性粒细胞。
结论:我们首次表明,过敏和吸入性皮质类固醇的使用与哮喘患者气道中较低数量的IL-17 +细胞相关。重要的是,IL-17+细胞主要是中性粒细胞,这与淋巴细胞(Th17)是IL-17的主要来源相冲突。
(苏欣 审校)
PLoS One. 2016 Aug 23;11(8):e0161433. doi: 10.1371/journal.pone.0161433. eCollection 2016.
Atopy and Inhaled Corticosteroid Use Associate with Fewer IL-17+ Cells in Asthmatic Airways.
Fattahi F1,2,3,4, Brandsma CA2,3, Lodewijk M2,3, Reinders-Luinge M2,3, Postma DS1,3, Timens W2,3, Hylkema MN2,3, Ten Hacken NH1,3.
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Abstract
BACKGROUND:Interleukin (IL)-17 plays a critical role in numerous immune and inflammatory responses and was recently suggested to contribute to the pathogenesis of nonatopic (non-eosinophil/neutrophil-dominant) asthma. We aimed to compare expression of IL-17 in bronchial airways between atopic and nonatopic asthmatics, with/without inhaled corticosteroid (ICS) use and to identify its major cellular source.
METHODS:Bronchial biopsies from 114 patients with mild-to-moderate asthma were investigated: 33 nonatopic, 63 non-corticosteroid users, 90 nonsmokers. IL-17 expression was correlated with atopy and inflammatory cell counts (EPX, NP57, CD3, CD4, CD8, CD20, CD68), taking ICS use and smoking into account. Multiple linear regression analyses were used to determine the independent factors as well as the most relevant inflammatory cells contributing to IL-17 expression. Double immunostainings were performed to confirm the major cellular source of IL-17.
RESULTS:In non-ICS users, nonatopic asthmatics had more IL-17+ cells in the airway wall than atopic asthmatics. In both atopic and nonatopic asthmatics, ICS use was associated with lower numbers of IL-17+ cells, independent of smoking. The number of IL-17+ cells was associated with the number of neutrophils (B: 0.26, 95% CI: 0.17-0.35) and eosinophils (B: 0.18, 95% CI: 0.07-0.29). The majority of IL-17+ cells were neutrophils, as confirmed by double immunostaining.
CONCLUSIONS:We show for the first time that atopy and ICS use are associated with lower numbers of IL-17+ cells in asthmatic airways. Importantly, IL-17+ cells were mostly neutrophils which conflicts with the paradigm that lymphocytes (Th17) are the main source of IL-17.
PLoS One. 2016 Aug 23;11(8):e0161433. doi: 10.1371/journal.pone.0161433. eCollection 2016.