Interleukin 17A (IL-17A), mainly produced by the T helper subclass Th17, plays a key role in the psoriatic plaque formation and progression. The clinical effectiveness of anti-IL-17A agents is documented, but the early and specific mechanisms of their protection are not identified yet. The challenge of the present study is to investigate the possible reversal exerted by a specific anti-IL-17A agent on the psoriatic events induced by IL-17A in a three-dimensional organotypic model of normal human skin. Bioptic skin fragments obtained after aesthetic surgery of healthy women (n=5) were incubated with i) IL-17A biological inhibitor (anti-IL-17A), ii) IL-17A, iii) a combination of IL-17A and its specific IL-17A biological inhibitor (COMBO). A Control group was in parallel cultured and incubation lasted for 24 and 48 h epidermal-side-up at the air-liquid interface. All subjects were represented in all experimental groups at all considered time-points. Keratinocyte proliferation and the presence of epidermal Langerhans cells were quantitatively estimated. In parallel with transmission electron microscopy analysis, immunofluorescence studies for the epidermal distribution of keratin (K)10, K14, K16, K17, filaggrin/occludin, Toll-like Receptor 4, and Nuclear Factor kB were performed. IL-17A inhibited cell proliferation and induced K17 expression, while samples incubated with the anti-IL-17A agent were comparable to controls. In the COMBO group the IL-17A-induced effects were almost completely reverted. Our study, for the first time, elucidates the most specific psoriatic cellular events that can be partially affected or completely reverted by a specific anti-IL-17A agent during the early phases of the plaque onset and progression. On the whole, this work contributes to expand the knowledge of the psoriatic tableau.

中文翻译：

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在正常人皮肤培养的三维器官模型中，由白介素17诱导的银屑病转移迅速被特定的抗IL-17A剂逆转。

白细胞介素17A（IL-17A）主要由T辅助亚类Th17产生，在银屑病斑块的形成和发展中起关键作用。有文献记载了抗IL-17A药物的临床有效性，但尚未确定其早期和特定的保护机制。本研究的挑战是研究在正常人皮肤的三维器官模型中，特定的抗IL-17A试剂对IL-17A诱导的银屑病的逆转作用。将健康女性（n = 5）进行美容手术后获得的活检皮肤碎片与i）IL-17A生物抑制剂（anti-IL-17A），ii）IL-17A，iii）IL-17A及其特异性结合物一起孵育IL-17A生物抑制剂（COMBO）。对照组进行平行培养，并在气液界面持续培养表皮朝上24和48小时。所有受试者均在所有考虑的时间点参加所有实验组。定量估计角质形成细胞增殖和表皮朗格汉斯细胞的存在。与透射电子显微镜分析并行，对角蛋白（K）10，K14，K16，K17，丝蛋白/封闭蛋白，Toll样受体4和核因子kB的表皮分布进行了免疫荧光研究。IL-17A抑制细胞增殖并诱导K17表达，而用抗IL-17A试剂孵育的样品与对照组相当。在COMBO组中，IL-17A诱导的作用几乎完全恢复。我们的研究是第一次 阐明了在斑块起病和发展的早期阶段，特定抗IL-17A药物可部分影响或完全逆转的最特异性银屑病细胞事件。总体而言，这项工作有助于扩大银屑病画面的知识。