Tight junctions are important for skin barrier function. The tight junction protein claudin 1 (Cldn-1) has been reported to be down-regulated in nonlesional skin of atopic dermatitis (AD) patients. In contrast, we did not observe a significant down-regulation of Cldn-1 in nonlesional skin of the AD cohort used in this study. However, for the first time, a significant down-regulation of Cldn-1 in the upper and lower epidermal layers of lesional skin was detected. In addition, there was a significant up-regulation of Cldn-4 in nonlesional, but not lesional, AD skin. For occludin, no significant alterations were observed. In an AD-like allergic dermatitis mouse model, Cldn-1 down-regulation in eczema was significantly influenced by dermal inflammation, and significantly correlated with hallmarks of eczema (ie, increased keratinocyte proliferation, altered keratinocyte differentiation, increased epidermal thickness, and impaired barrier function). In human epidermal equivalents, the addition of IL-4, IL-13, and IL-31 resulted in a down-regulation of Cldn-1, and Cldn1 knockdown in keratinocytes resulted in abnormal differentiation. In summary, we provide the first evidence that Cldn-1 and Cldn-4 are differentially involved in AD pathogenesis. Our data suggest a role of Cldn-1 in AD eczema formation triggered by inflammation.

中文翻译：

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异位性皮炎中claudin-1和claudin-4的不同调节。

紧密连接对于皮肤屏障功能很重要。据报道，特应性皮炎（AD）患者的非病变皮肤中紧密连接蛋白claudin 1（Cldn-1）的表达下调。相比之下，我们没有在本研究中使用的AD队列的非病变皮肤中观察到Cldn-1的显着下调。但是，第一次，在病变皮肤的上表皮层和下表皮层中检测到了Cldn-1的显着下调。此外，在非病变性但非病变性AD皮肤中，Cldn-4明显上调。对于occludin，未观察到明显的改变。在类似AD的变应性皮炎小鼠模型中，湿疹中Cldn-1的下调受到皮肤炎症的显着影响，并且与湿疹的特征显着相关（即，角质形成细胞增殖增加，角质形成细胞分化改变，表皮厚度增加和屏障功能受损）。在人类表皮等效物中，IL-4，IL-13和IL-31的添加导致Cldn-1的下调，而角质形成细胞中Cldn1的敲低导致异常分化。总而言之，我们提供了Cldn-1和Cldn-4差异参与AD发病机制的第一个证据。我们的数据表明Cldn-1在炎症触发的AD湿疹形成中的作用。我们提供了第一个证据，表明Cldn-1和Cldn-4参与AD发病机制的差异。我们的数据表明Cldn-1在炎症触发的AD湿疹形成中的作用。我们提供了第一个证据，表明Cldn-1和Cldn-4参与AD发病机制的差异。我们的数据表明Cldn-1在炎症触发的AD湿疹形成中的作用。