ITGB4 deficiency in airway epithelia enhances HDM-induced airway inflammation through hyperactivation of TLR4 signaling pathway
ITGB4 deficiency in airway epithelia enhances HDM-induced airway inflammation through hyperactivation of TLR4 signaling pathway
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DOI：
10.1093/jleuko/qiac013
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发表时间：
2023-02-01
影响因子：
5.5
通讯作者：
Liu，Chi
中科院分区：
文献类型：
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作者：
Zhou，Kai;Yuan，Lin;Liu，Chi
呼吸道上皮细胞(AECs)是呼吸系统抵抗外界刺激的第一道屏障，在哮喘的发生发展中起着至关重要的作用。已知血管内皮细胞在哮喘易感性和严重程度中起关键作用。ITGB4是哮喘患者呼吸道上皮细胞中一种下调的黏附分子，参与了变态反应刺激后肺组织炎症的加重。AECs中的Toll样受体4(TLR4)也被证明在哮喘患者肺部炎症的发生发展中起关键作用。然而，TLR4在血管内皮细胞中的具体内在调控机制尚不清楚。在这篇文章中，我们证明了AECs中ITGB4的缺乏通过抑制FYN的磷酸化来增强TLR4信号通路的过度激活，从而加强了HDM诱导的气道炎症。此外，TLR4拮抗剂治疗或阻断FYN可分别抑制或加重HDM应激ITGB4缺陷小鼠的肺部炎症。综上所述，这些结果表明AECs中ITGB4缺乏通过ITGB4-FYN-TLR4轴增强HDM诱导的肺炎症反应，这可能为哮喘的肺部炎症治疗提供新的治疗途径。
Airway epithelial cells (AECs) are the first cell barrier of the respiratory system against external stimuli that play a critical role in the development of asthma. It is known that AECs play a key role in asthma susceptibility and severity. ITGB4 is a downregulated adhesion molecule in the airway epithelia of asthma patients, which was involved in the exaggerated lung inflammation after allergy stimulation. Toll-like receptor 4 (TLR4) in AECs has also been shown to play a crucial role in the development of lung inflammation in asthma patients. However, the specific intrinsic regulatory mechanism of TLR4 in AECs are still obscure. In this article, we demonstrated that ITGB4 deficiency in AECs enhances HDM-induced airway inflammation through hyperactivation of the TLR4 signaling pathway, which is mediated by inhibition of FYN phosphorylation. Moreover, TLR4-antagonist treatment or blockade of FYN can inhibit or exaggerate lung inflammation in HDM-stressed ITGB4-deficient mice, separately. Together, these results demonstrated that ITGB4 deficiency in AECs enhances HDM-induced lung inflammatory response through the ITGB4-FYN-TLR4 axis, which may provide new therapeutic approaches for the management of lung inflammation in asthma.