Centro Malattie Apparato Digerente (CEMAD) Digestive Disease Center, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Università Cattolica del Sacro Cuore, 00168 Roma, Italy.
Department of Basic Medical Sciences, Neuroscience and Sense Organs, Section of Respiratory Disease, University "Aldo Moro" of Bari, 70121 Bari, Italy.
Int J Mol Sci. 2024 May 25;25(11):5747. doi: 10.3390/ijms25115747.
Epithelial barrier damage plays a central role in the development and maintenance of allergic inflammation. Rises in the epithelial barrier permeability of airways alter tissue homeostasis and allow the penetration of allergens and other external agents. Different factors contribute to barrier impairment, such as eosinophilic infiltration and allergen protease action-eosinophilic cationic proteins' effects and allergens' proteolytic activity both contribute significantly to epithelial damage. In the airways, allergen proteases degrade the epithelial junctional proteins, allowing allergen penetration and its uptake by dendritic cells. This increase in allergen-immune system interaction induces the release of alarmins and the activation of type 2 inflammatory pathways, causing or worsening the main symptoms at the skin, bowel, and respiratory levels. We aim to highlight the molecular mechanisms underlying allergenic protease-induced epithelial barrier damage and the role of immune response in allergic asthma onset, maintenance, and progression. Moreover, we will explore potential clinical and radiological biomarkers of airway remodeling in allergic asthma patients.
上皮屏障损伤在过敏炎症的发生和维持中起着核心作用。气道上皮屏障通透性的增加会改变组织的动态平衡，使过敏原和其他外源性物质穿透。不同的因素导致屏障损伤，如嗜酸性粒细胞浸润和过敏原蛋白酶作用——嗜酸性阳离子蛋白的作用和过敏原的蛋白水解活性都显著导致上皮损伤。在气道中，过敏原蛋白酶降解上皮连接蛋白，使过敏原穿透并被树突状细胞摄取。这种过敏原-免疫系统相互作用的增加会导致警报素的释放和 2 型炎症途径的激活，导致或加重皮肤、肠道和呼吸道的主要症状。我们旨在强调过敏原蛋白酶诱导的上皮屏障损伤的分子机制，以及免疫反应在过敏性哮喘发病、维持和进展中的作用。此外，我们将探讨过敏性哮喘患者气道重塑的潜在临床和放射学标志物。
