Epithelial barrier function: at the front line of asthma immunology and allergic airway inflammation.
Epithelial barrier function: at the front line of asthma immunology and allergic airway inflammation.
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DOI：
10.1016/j.jaci.2014.05.049
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发表时间：
2014-09
影响因子：
14.2
通讯作者：
Rezaee, Fariba
中科院分区：
文献类型：
--
作者：
Georas, Steve N.;Rezaee, Fariba
关键词：
气道上皮细胞形成与外界的屏障，处于粘膜免疫的前线。上皮顶端连接复合物是促进细胞-细胞粘附和屏障完整性的多蛋白亚基。最近在皮肤和胃肠道中的研究表明，细胞-细胞连接的破坏是启动上皮免疫应答所必需的，但这如何适用于肺中的粘膜免疫尚不清楚。越来越多的证据表明，上皮屏障功能缺陷是哮喘气道炎症的一个特征。这一领域的一个挑战是，屏障功能和连接的完整性很难在完整的肺研究，但创新的方法应该在不久的将来提供新的知识在这一领域。在这篇文章中，我们回顾了上皮顶端连接复合物的结构和功能，强调上皮屏障的调节如何影响先天性和适应性免疫。我们讨论了为什么有缺陷的上皮屏障功能可能与哮喘中的Th 2极化有关，并提出了一种屏障功能障碍的变阻器模型，该模型涉及吸入过敏原颗粒的大小作为影响适应性免疫的重要因素。
Airway epithelial cells form a barrier to the outside world, and are at the frontline of mucosal immunity. Epithelial apical junctional complexes are multi-protein subunits that promote cell-cell adhesion and barrier integrity. Recent studies in the skin and GI tract suggest that disruption of cell-cell junctions is required to initiate epithelial immune responses, but how this applies to mucosal immunity in the lung is not clear. Increasing evidence indicates that defective epithelial barrier function is a feature of airway inflammation in asthma. One challenge in this area is that barrier function and junctional integrity are difficult to study in the intact lung, but innovative approaches should provide new knowledge in this area in the near future. In this article, we review the structure and function of epithelial apical junctional complexes, emphasizing how regulation of the epithelial barrier impacts innate and adaptive immunity. We discuss why defective epithelial barrier function may be linked to Th2 polarization in asthma, and propose a rheostat model of barrier dysfunction that implicates the size of inhaled allergen particles as an important factor influencing adaptive immunity.
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