Airway epithelial ITGB4 deficiency in early life mediates pulmonary spontaneous inflammation and enhanced allergic immune response
Airway epithelial ITGB4 deficiency in early life mediates pulmonary spontaneous inflammation and enhanced allergic immune response
复制标题
生命早期气道上皮ITGB4缺乏介导肺部自发炎症并增强过敏性免疫反应
DOI：
10.1111/jcmm.15000
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发表时间：
2020-01
影响因子：
5.3
通讯作者：
Liu Chi
中科院分区：
文献类型：
--
作者：
Tang Sha;Du Xizi;Yuan Lin;Xiao Gelei;Wu Mengping;Wang Leyuan;Wu ShuangYan;Duan Zhen;Xiang Yang;Qu Xiangping;Liu Huijun;Zou Yizhou;Qin Xiaoqun;Qin Ling;Liu Chi
肺对呼吸道病原体和过敏原的免疫反应在生命早期启动，这将进一步影响哮喘的后期发作。气道上皮细胞是机体对过敏性刺激和环境污染物的第一道机械物理屏障，也是肺免疫应答启动和发展的关键调节因子。然而，早期肺免疫应答的上皮调节机制还远未清楚。本课题组前期研究发现，整合素β4（integrin β 4，ITGB 4）在哮喘患者气道上皮细胞中表达减少，并存在特异性变异位点。成年小鼠ITGB 4缺乏加重了肺Th2免疫应答，并增强了屋尘螨（HDM）诱导的哮喘模型的气道高反应性（AHR）。然而，ITGB 4对出生后肺免疫应答的贡献仍然不清楚。在这里，我们进一步证明了出生后ITGB 4缺乏介导了ILC2活化和嗜酸性粒细胞和淋巴细胞浸润增加的自发性肺部炎症。此外，ITGB4缺陷通过EGFR途径调节气道上皮细胞中胸腺基质淋巴细胞生成素（TSLP）的产生。TSLP的中和显著抑制ITGB 4缺陷小鼠中的自发性炎症。此外，我们还发现ITGB 4缺乏导致对HDM应激的肺变应性炎症反应加剧。总之，这些发现表明，生命早期的ITGB 4缺乏导致自发性肺部炎症，并诱导对HDM吸入性变应原的过度肺部炎症反应。
Lung immune responses to respiratory pathogens and allergens are initiated in early life which will further influence the later onset of asthma. The airway epithelia form the first mechanical physical barrier to allergic stimuli and environmental pollutants, which is also the key regulator in the initiation and development of lung immune response. However, the epithelial regulation mechanisms of early‐life lung immune responses are far from clear. Our previous study found that integrin β4 (ITGB4) is decreased in the airway epithelium of asthma patients with specific variant site. ITGB4 deficiency in adult mice aggravated the lung Th2 immune responses and enhanced airway hyper‐responsiveness (AHR) with a house dust mite (HDM)‐induced asthma model. However, the contribution of ITGB4 to the postnatal lung immune response is still obscure. Here, we further demonstrated that ITGB4 deficiency following birth mediates spontaneous lung inflammation with ILC2 activation and increased infiltration of eosinophils and lymphocytes. Moreover, ITGB4 deficiency regulated thymic stromal lymphopoietin (TSLP) production in airway epithelial cells through EGFR pathways. Neutralization of TSLP inhibited the spontaneous inflammation significantly in ITGB4‐deficient mice. Furthermore, we also found that ITGB4 deficiency led to exaggerated lung allergic inflammation response to HDM stress. In all, these findings indicate that ITGB4 deficiency in early life causes spontaneous lung inflammation and induces exaggerated lung inflammation response to HDM aeroallergen.
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影响因子：
--
作者：
Soung YH;Korneeva N;Kim TH;Chung J
通讯作者：
Chung J
DOI：
10.1126/science.1219328
发表时间：
2012-04-27
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
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通讯作者：
Blumberg RS
影响因子：
7.4
作者：
Mahmutovic Persson I;Akbarshahi H;Menzel M;Brandelius A;Uller L
通讯作者：
Uller L
DOI：
10.4049/jimmunol.1601950
发表时间：
2018-01
期刊：
The Journal of Immunology
影响因子：
--
作者：
T. H. Nguyen;S. Maltby;H. Tay;F. Eyers;P. Foster;Ming Yang
通讯作者：
T. H. Nguyen;S. Maltby;H. Tay;F. Eyers;P. Foster;Ming Yang
DOI：
10.1016/b978-0-12-409527-4.00001-8
发表时间：
1984
期刊：
Techniques in The Behavioral and Neural Sciences
影响因子：
--
作者：
J. Fox;B. J. Cohen;F. Loew
通讯作者：
J. Fox;B. J. Cohen;F. Loew