ITGB4 is essential for containing HDM-induced airway inflammation and airway hyperresponsiveness
ITGB4 is essential for containing HDM-induced airway inflammation and airway hyperresponsiveness
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ITGB4 对于抑制 HDM 诱导的气道炎症和气道高反应性至关重要
DOI：
10.1002/jlb.3a1017-411rr
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发表时间：
2018-05-01
影响因子：
5.5
通讯作者：
Qin, Xiaoqun
中科院分区：
文献类型：
--
作者：
Liu, Chi;Yuan, Lin;Qin, Xiaoqun
气道上皮细胞在哮喘的发病机制中发挥着重要作用。尽管气道上皮细胞的结构和功能缺陷被认为会增加哮喘易感性并加剧哮喘严重程度，但这些缺陷的机制和含义仍不确定。整合素 4 (ITGB4) 是一种结构粘附分子，在哮喘患者的气道上皮中表达下调。在这项研究中，我们证明 ITGB4 缺乏会导致小鼠严重的过敏性气道炎症和气道高反应性 (AHR)。屋尘螨 (HDM) 攻击后，与野生型小鼠相比，上皮细胞特异性 ITGB4 缺失小鼠的肺部淋巴细胞、嗜酸性粒细胞和中性粒细胞浸润增加。 ITGB4缺陷还导致HDM攻击后肺组织和T细胞中Th2细胞因子IL-4、IL-13和Th17细胞因子IL-17A的表达增加。 ITGB4缺陷小鼠炎症加重的部分原因是HDM应激后上皮屏障完整性受损，导致气道上皮细胞胸腺基质淋巴细胞生成素分泌增加。因此，这项研究表明，ITGB4 在抑制过敏性哮喘中过敏原介导的肺部炎症和气道高反应性方面发挥着关键作用。ITGB4 缺陷通过破坏屏障功能和改变 TSLP 分泌而导致气道炎症。
Airway epithelial cells play a significant role in the pathogenesis of asthma. Although the structural and functional defects of airway epithelial cells have been postulated to increase asthma susceptibility and exacerbate asthma severity, the mechanism and implication of these defects remain uncertain. Integrin 4 (ITGB4) is a structural adhesion molecule that is downregulated in the airway epithelium of asthma patients. In this study, we demonstrated that ITGB4 deficiency leads to severe allergy-induced airway inflammation and airway hyper-responsiveness (AHR) in mice. After house dust mite (HDM) challenge, epithelial cell-specific ITGB4-deleted mice showed increased lymphocyte, eosinophil, and neutrophil infiltration into lung compared with that of the wild-type mice. ITGB4 deficiency also resulted in increased expression of the Th2 cytokine IL-4, IL-13, and the Th17 cytokine IL-17A in the lung tissue and in the T cells after HDM challenge. The aggravated inflammation in ITGB4 defect mice was partly caused by enhanced disrupted epithelial barrier integrity after HDM stress, which induced the increased thymic stromal lymphopoietin secretion from airway epithelial cells. This study therefore demonstrates that ITGB4 plays a pivotal role in containing allergen-mediated lung inflammation and airway hyper-responsiveness in allergic asthma.ITGB4 defects conferred airway inflammation by disrupting barrier function and altering TSLP secretion.