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E-Cadherin is Dispensable to Maintain Langerhans Cells in the Epidermis.
Journal of Investigative Dermatology ( IF 6.5 ) Pub Date : 2019-06-28 , DOI: 10.1016/j.jid.2019.06.132
Anna Brand 1 , Nathalie Diener 1 , Sonja P Zahner 2 , Christoph Tripp 3 , Ronald A Backer 1 , Khalad Karram 1 , Aimin Jiang 4 , Ira Mellman 5 , Patrizia Stoitzner 3 , Björn E Clausen 1
Affiliation  

The cell adhesion molecule E-cadherin is a major component of adherens junctions and marks Langerhans cells (LC), the only dendritic cell (DC) population of the epidermis. LC form a dense network and attach themselves to the surrounding keratinocytes via homophilic E-cadherin binding. LC activation, mobilization, and migration require a reduction in LC E-cadherin expression. To determine whether E-cadherin plays a role in regulating LC homeostasis and function, we generated CD11c-specific E-cadherin knockout mice (CD11c-Ecaddel). In the absence of E-cadherin-mediated cell adhesion, LC numbers remained stable and similar as in control mice, even in aged animals. Intriguingly, E-cadherin-deficient LC displayed a dramatically changed morphology characterized by a more rounded cell body and fewer dendrites than wild-type cells. Nevertheless, maturation and migration of LC lacking E-cadherin was not altered, neither under steady-state nor inflammatory conditions. Accordingly, CD11c-Ecaddel and control mice developed comparable contact hypersensitivity reactions and imiquimod-triggered psoriatic skin inflammation, indicating that E-cadherin on LC does not influence their ability to orchestrate T cell-mediated immunity. In conclusion, our data demonstrate that E-cadherin is dispensable to maintain LC in the epidermis and does not regulate LC maturation, migration, and function.

中文翻译:

E-钙粘蛋白对于维持表皮中的朗格汉斯细胞是可有可无的。

细胞粘附分子 E-钙粘蛋白是粘附连接的主要成分,并标记朗格汉斯细胞 (LC),这是表皮中唯一的树突状细胞 (DC) 群。LC 形成一个密集的网络,并通过同质 E-钙粘蛋白结合将自身附着到周围的角质形成细胞上。LC 激活、动员和迁移需要降低 LC E-钙粘蛋白的表达。为了确定 E-cadherin 是否在调节 LC 稳态和功能中起作用,我们生成了 CD11c 特异性 E-cadherin 敲除小鼠 (CD11c-Ecaddel)。在没有 E-钙粘蛋白介导的细胞粘附的情况下,LC 数量保持稳定且与对照小鼠相似,即使在老年动物中也是如此。有趣的是,缺乏 E-钙粘蛋白的 LC 显示出显着变化的形态,其特征是比野生型细胞更圆的细胞体和更少的树突。尽管如此,缺乏 E-钙粘蛋白的 LC 的成熟和迁移没有改变,无论是在稳态还是炎症条件下。因此,CD11c-Ecaddel 和对照小鼠发生了类似的接触超敏反应和咪喹莫特引发的银屑病皮肤炎症,表明 LC 上的 E-钙粘蛋白不影响它们协调 T 细胞介导免疫的能力。总之,我们的数据表明,E-钙粘蛋白对于维持表皮中的 LC 是可有可无的,并且不调节 LC 的成熟、迁移和功能。表明 LC 上的 E-钙粘蛋白不影响它们协调 T 细胞介导的免疫的能力。总之,我们的数据表明,E-钙粘蛋白对于维持表皮中的 LC 是可有可无的,并且不调节 LC 的成熟、迁移和功能。表明 LC 上的 E-钙粘蛋白不影响它们协调 T 细胞介导的免疫的能力。总之,我们的数据表明,E-钙粘蛋白对于维持表皮中的 LC 是可有可无的,并且不调节 LC 的成熟、迁移和功能。
更新日期:2019-12-19
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