Etiology of epithelial barrier dysfunction in patients with type 2 inflammatory diseases.
Etiology of epithelial barrier dysfunction in patients with type 2 inflammatory diseases.
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DOI：
10.1016/j.jaci.2017.04.010
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发表时间：
2017-06
期刊：
影响因子：
--
通讯作者：
Berdnikovs S
中科院分区：
文献类型：
--
作者：
Schleimer RP;Berdnikovs S
皮肤、胃肠道和呼吸道的上皮屏障具有共同的关键功能，如维持针对环境侮辱和过敏原的物理屏障，以及提供平衡内部和外部环境之间沟通的组织界面。我们现在了解到，在过敏性疾病中，无论组织位置如何，上皮屏障的动态平衡偏向于分化丧失、连接完整性降低和先天防御受损。重要的是，以这些特征为特征的上皮功能障碍似乎是变态反应和过敏性疾病发展的先兆。尽管我们越来越认识到屏障功能障碍在引发变态反应性疾病中的中心作用，但关于破坏正常屏障功能的机制仍有许多重要的问题需要回答。虽然我们的外部环境(蛋白水解酶、过敏原、损伤)通常被认为是与过敏反应相关的屏障破坏的主要因素，但有必要更好地了解内部环境(激素、饮食、生物钟)的作用。疾病的系统性驱动因素，如内分泌系统的改变、新陈代谢和发育信号的异常控制，正在成为推动各种屏障位置的上皮功能障碍和过敏易感性的新参与者。使用系统生物学工具和因果关系驱动的实验室实验，识别这种上皮功能障碍的中心介质，对于建立新的战略干预措施以防止或逆转过敏屏障丧失的过程至关重要。
Epithelial barriers of the skin, gastrointestinal tract and airway serve common critical functions such as maintaining a physical barrier against environmental insults and allergens, as well as providing a tissue interface balancing the communication between the internal and external environments. We now understand that in allergic disease, regardless of tissue location, the homeostatic balance of the epithelial barrier is skewed towards loss of differentiation, reduced junctional integrity and impaired innate defense. Importantly, epithelial dysfunction characterized by these traits appears to pre-date atopy and development of allergic disease. Despite our growing appreciation of the centrality of barrier dysfunction in the initiation of allergic disease, many important questions remain to be answered regarding the mechanisms disrupting the normal barrier function. Although our external environment (proteases, allergens, injury) is classically thought of as a principal contributor to barrier disruption associated with allergic sensitization, there is a need to better understand contributions of the internal environment (hormones, diet, circadian clock). Systemic drivers of disease, such as alterations of the endocrine system, metabolism and aberrant control of developmental signaling, are emerging as new players in driving epithelial dysfunction and allergic predisposition at various barrier sites. Identifying such central mediators of epithelial dysfunction, using both systems biology tools and causality-driven laboratory experimentation, will be essential in building new strategic interventions to prevent or reverse the process of barrier loss in allergy.
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影响因子：
14.2
作者：
De Benedetto, Anna;Rafaels, Nicholas M;McGirt, Laura Y;Ivanov, Andrei I;Georas, Steve N;Cheadle, Chris;Berger, Alan E;Zhang, Kunzhong;Vidyasagar, Sadasivan;Yoshida, Takeshi;Boguniewicz, Mark;Hata, Tissa;Schneider, Lynda C;Hanifin, Jon M;Gallo, Richard L;Novak, Natalija;Weidinger, Stephan;Beaty, Terri H;Leung, Donald Y M;Barnes, Kathleen C;Beck, Lisa A
通讯作者：
Beck, Lisa A
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4
作者：
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作者：
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影响因子：
2.7
作者：
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通讯作者：
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DOI：
10.1016/s1357-2725(02)00048-1
发表时间：
2002-12-01
影响因子：
4
作者：
Davies, DE;Holgate, ST
通讯作者：
Holgate, ST