Abstract：
(1) Background: Atopic dermatitis is one of the most common inflammatory skin diseases characterized by T helper (Th) 2 and Th22 cells producing interleukin (IL)-4/IL-13 and IL-22, respectively. The specific contribution of each cytokine to the impairment of the physical and the immune barrier via Toll-like receptors (TLRs) is poorly addressed concerning the epidermal compartment of the skin. (2) Methods: The effect of IL-4, IL-13, IL-22, and the master cytokine IL-23 is evaluated in a 3D model of normal human skin biopsies (n = 7) at the air-liquid interface for 24 and 48 h. We investigated by immunofluorescence the expressions of (i) claudin-1, zonula occludens (ZO)-1 filaggrin, involucrin for the physical barrier and (ii) TLR2, 4, 7, 9, human beta-defensin 2 (hBD-2) for the immune barrier. (3) Results: Th2 cytokines induce spongiosis and fail in impairing tight junction composition, while IL-22 reduces and IL-23 induces claudin-1 expression. IL-4 and IL-13 affect the TLR-mediated barrier largely than IL-22 and IL-23. IL-4 early inhibits hBD-2 expression, while IL-22 and IL-23 induce its distribution. (4) Conclusions: This experimental approach looks to the pathogenesis of AD through molecular epidermal proteins rather than cytokines only and paves the way for tailored patient therapy.
摘要：
（1）背景：特应性皮炎是最常见的炎症性皮肤病之一，其特征是T辅助细胞（Th）2和Th22细胞分别产生白细胞介素（IL）-4/IL-13和IL-22。关于皮肤的表皮区室，每种细胞因子通过Toll样受体（TLR）对物理和免疫屏障的损害的具体贡献很少解决。（2）方法：IL-4，IL-13，IL-22和主细胞因子IL-23的作用在正常人皮肤活检的3D模型（n=7）中在气-液界面进行24和48小时。我们通过免疫荧光研究了（i）claudin-1，成虫带（ZO）-1的表达，总蛋白用于物理屏障和（ii）TLR2，4，7，9，人β-防御素2（hBD-2）用于免疫屏障。（3）结果：Th2细胞因子诱导海绵体，并在损害紧密连接组成失败，而IL-22减少和IL-23诱导claudin-1表达。IL-4和IL-13比IL-22和IL-23更影响TLR介导的屏障。IL-4早期抑制hBD-2表达，而IL-22和IL-23诱导其分布。（4）结论：该实验方法通过分子表皮蛋白而不是仅通过细胞因子来研究AD的发病机理，并为量身定制的患者治疗铺平了道路。
