Vaher Helen, Gadsbøll Anne-Sofie Ø, Seibel Alexandra T, Kongsbak-Wismann Martin, Lohmann Rebecca K D, Mraz Veronika, Funch Anders B, Jee Mia H, Ødum Niels, Woetmann Anders, Geisler Carsten, Bonefeld Charlotte M
The LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Allergy. 2025 Jul;80(7):1956-1966. doi: 10.1111/all.16421. Epub 2024 Dec 14.
Dysfunction 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 (T) cells play a central role in the immune response to contact allergens. However, if and how allergen-specific CD8 T cells affect the expression of skin barrier molecules is not known.
The 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.
Sensitization with the contact allergen 1-fluoro-2,4-dinitrobenzene (DNFB) resulted in epidermal accumulation of CD8 T 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.
CD8 T 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.
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细胞在对接触性过敏原的免疫反应中起核心作用。然而，过敏原特异性CD8 T细胞是否以及如何影响皮肤屏障分子的表达尚不清楚。
在ACD小鼠模型中，通过RT-qPCR和免疫荧光法测定皮肤屏障分子的表达水平。通过清除CD8细胞研究CD8 T细胞对皮肤屏障分子表达的作用。使用人原代角质形成细胞评估IFN-γ和接触性过敏原对其皮肤屏障分子表达的直接影响。
用接触性过敏原1-氟-2,4-二硝基苯（DNFB）致敏导致CD8 T细胞在表皮积聚，即使在炎症反应完全宏观缓解后，Ifng仍持续上调，角蛋白5（Krt5）和角蛋白14（Krt14）仍持续下调。用DNFB激发导致Krt5和Krt14进一步快速下调以及其他几种皮肤屏障分子的下调。清除CD8细胞消除了皮肤屏障分子的持续和快速下调。在角质形成细胞中，IFN-γ和接触性过敏原协同下调KRT5和KRT14的表达。
CD8 T细胞导致皮肤屏障分子表达持续降低，这可能会在皮肤随后接触过敏原和抗原时加剧过敏原渗透和炎症反应。
