Epithelial Interleukin-25 Is a Key Mediator in Th2-High, Corticosteroid-Responsive Asthma
Epithelial Interleukin-25 Is a Key Mediator in Th2-High, Corticosteroid-Responsive Asthma
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上皮白细胞介素 25 是 Th2 高、皮质类固醇反应性哮喘的关键介质
DOI：
10.1164/rccm.201403-0505oc
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发表时间：
2014-09-15
影响因子：
24.7
通讯作者：
Zhen, Guohua
中科院分区：
文献类型：
--
作者：
Cheng, Dan;Xue, Zheng;Zhen, Guohua
原理：2型细胞因子通路的激活在大部分哮喘受试者中起着核心作用。Th 2-高和Th 2-低哮喘具有不同的临床、病理和分子表型，并且对治疗的反应不同。目的：探讨上皮细胞因子IL-25、IL-33和胸腺基质淋巴细胞生成素的表达是否与哮喘2型反应有关，并预测哮喘对吸入性皮质类固醇（ICS）的反应。我们分析了21名健康对照受试者和43名哮喘受试者的肺功能检查、血液和支气管镜活检。哮喘受试者进行了为期8周的治疗吸入布地奈德。测量和主要结果：上皮细胞表达的IL-25，但不是IL-33或胸腺基质淋巴细胞生成素，增加了一个子集的哮喘受试者。高IL-25亚群具有更高的气道高反应性、更多的气道和血液嗜酸性粒细胞、更高的血清IgE、更多的上皮下增厚和更高的Th 2特征基因表达。ICS改善了IL-25高亚组的FEV 1和高反应性，但对IL-25低亚组无影响。血浆IL-25水平与上皮细胞IL-25表达，气道嗜酸性粒细胞增多症，和有益的反应ICS treatment.Conclusions：IL-25测量确定两个子集的主题具有不同的哮喘表型和不同的反应ICS。由于IL-25在触发2型反应中起主要作用，因此支气管上皮IL-25表达可能是哮喘2型反应激活的关键决定因素。血浆IL-25水平反映了气道IL-25/2型反应的激活，并可用于预测哮喘治疗的反应。
Rationale: Activation of type 2 cytokine pathways plays a central role in a large subset of subjects with asthma. Th2-high and Th2-low asthma have distinct clinical, pathologic, and molecular phenotypes and respond differently to therapy. The factors that initiate type 2 responses in some subjects with asthma are unknown.Objectives: To determine whether expression of epithelial cytokines IL-25, IL-33, and thymic stromal lymphopoietin are associated with type 2 responses and predict response to inhaled corticosteroid (ICS) in asthma.Methods: We analyzed pulmonary function tests, blood, and bronchoscopic biopsies from 21 healthy control subjects and 43 subjects with asthma. Subjects with asthma underwent an 8-week treatment with inhaled budesonide.Measurements and Main Results: Epithelial expression of IL-25, but not IL-33 or thymic stromal lymphopoietin, was increased in a subset of subjects with asthma. The IL-25-high subset had greater airway hyperresponsiveness, more airway and blood eosinophils, higher serum IgE, more subepithelial thickening, and higher expression of Th2 signature genes. ICS improved FEV1 and hyperresponsiveness in the IL-25-high but not the IL-25-low subset. Plasma IL-25 levels correlated with epithelial IL-25 expression, airway eosinophilia, and beneficial responses to ICS treatment.Conclusions: IL-25 measurements identify two subsets of subjects with distinct asthma phenotypes and different responses to ICS. Because IL-25 has a major role in triggering type 2 responses, bronchial epithelial IL-25 expression is likely a key determinant of type 2 response activation in asthma. Plasma IL-25 level reflects airway IL-25/type 2 response activation and may be useful for predicting responses to asthma therapy.