ITGB4is essential for containing HDM-induced airway inflammation and airway hyperresponsiveness

Abstract

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 β4 (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.

Respiratory syncytial virus infection‐induced mucus secretion by down‐regulation of miR‐34b/c‐5p expression in airway epithelial cells

“…RT‐PCR was conducted according to the PrimeScript™ RT Master Mix Kit (Takara, Japan). Quantitative PCR (qPCR) was performed on a CFX96 Touch™ Deep Well Real‐Time PCR Detection System (Bio‐rad, USA) by the use of TB Green ® Premix Ex Taq (Takara, Japan) with thermal cycling conditions 24 . Primer sequences were described in Supplementary Table 1.…”

ITGB4 deficiency induces senescence of airway epithelial cells through p53 activation

“…To avoid lethal effect of ITGB4 null mice, we constructed a conditional ITGB4 deficiency model: CCSP–rtTA tg/− /TetO‐Cre tg/− /ITGB4 fl/fl . In the model, ITGB4 was deleted only in the airway epithelial cells . Then, SA‐β‐gal was used to detect the senescence in airway epithelial cells .…”

“…Ozone‐challenged mice were stressed with ozone (2.0 ppm, 30 min) for 4 days and killed 12 h after the last exposure, whereas the control mice were treated with fresh air . The conditional ITGB4 knockout mice were constructed according to our previous procedures .…”

“…The long cytoplasmic domain of an ITGB4 subunit could recruit a series of signaling molecules and thereby influences the proliferation, damage repair and oxidative stress of epithelial cells . Besides, it has also been demonstrated that after house dust mite stress, ITGB4 defects in airway epithelial cells conferred increased airway hyper‐responsiveness and aggravated airway inflammation compared with wild‐type mice . Notably, ITGB4 has also been shown to be associated with senescence in many different cells .…”

Treatment of Microglia with Anti-PrP Antibodies Induces Neuronal Allergenicity

“…Liu and co-workers revealed that ITGB4 is involved in airway hyper-responsiveness and lung in ammation in allergic asthma. ITGB4-de cient mice displayed increased in ltration of lymphocyte, neutrophil, and eosinophil as well as expression of IL-4, IL-13, and IL-13A in lung tissue [89]. Tang et al showed that ITGB4-de ciency causes spontaneous exaggerated lung in ammation in early life [90].…”