BackgroundDysfunction of the skin barrier is regarded as a key event in the initiation and progression of inflammatory skin diseases. In many cases of allergic contact dermatitis (ACD), epidermal‐resident memory CD8+ T (TRM) cells play a central role in the immune response to contact allergens. However, if and how allergen‐specific CD8+ TRM cells affect the expression of skin barrier molecules is not known.MethodsThe expression level of skin barrier molecules was determined by RT‐qPCR and immunofluorescence in a mouse model of ACD. The role of CD8+ T cells on the expression of skin barrier molecules was investigated by depletion of CD8+ cells. Human primary keratinocytes were used to assess the direct effect of IFN‐γ and contact allergen on their expression of skin barrier molecules.ResultsSensitization with the contact allergen 1‐fluoro‐2,4‐dinitrobenzene (DNFB) resulted in epidermal accumulation of CD8+ TRM cells and prolonged upregulation of Ifng and downregulation of keratin 5 (Krt5) and Krt14 even after complete macroscopic remission of the inflammatory response. Challenge with DNFB lead to an additionally rapid downregulation of Krt5 and Krt14 and the downregulation of several other skin barrier molecules. Depletion of CD8+ cells abolished both the prolonged and rapid downregulation of skin barrier molecules. In keratinocytes, IFN‐γ and contact allergen synergistically down‐regulated the expression of KRT5 and KRT14.ConclusionCD8+ TRM cells contribute to a prolonged reduction in the expression of skin barrier molecules, which might exacerbate allergen permeation and the inflammatory response during succeeding exposures of the skin to allergens and antigens.

中文翻译：

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T 细胞在过敏性接触性皮炎小鼠模型中诱导屏障分子长时间下调


背景皮肤屏障功能障碍被认为是炎症性皮肤病发生和发展的关键事件。在许多过敏性接触性皮炎 （ACD） 病例中，表皮驻留记忆 CD8+ T （TRM） 细胞在对接触性过敏原的免疫反应中起着核心作用。然而，过敏原特异性 CD8+ TRM 细胞是否以及如何影响皮肤屏障分子的表达尚不清楚。方法采用 RT-qPCR 和免疫荧光法测定 ACD 小鼠模型中皮肤屏障分子的表达水平。通过耗竭 CD8 + 细胞来研究 CD8 + T 细胞对皮肤屏障分子表达的作用。人原代角质形成细胞用于评估 IFN-γ 和接触过敏原对其皮肤屏障分子表达的直接影响。结果接触过敏原 1-氟-2,4-二硝基苯 （DNFB） 致敏导致 CD8+ TRM 细胞表皮积累，Ifng 延长上调，角蛋白 5 （Krt5） 和 Krt14 下调，即使在炎症反应完全宏观缓解后也是如此。DNFB 的攻击导致 Krt5 和 Krt14 的额外快速下调以及其他几种皮肤屏障分子的下调。CD8 + 细胞的耗竭消除了皮肤屏障分子的长期和快速下调。在角质形成细胞中，IFN-γ 和接触过敏原协同下调 KRT5 和 KRT14 的表达。结论CD8 + TRM 细胞有助于皮肤屏障分子表达的长期降低，这可能会加剧皮肤连续暴露于过敏原和抗原期间的过敏原渗透和炎症反应。