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Abstract：
Interleukin (IL)-22 is a pro-inflammatory cytokine driving the progression of the psoriatic lesion with other cytokines, as Tumor Necrosis Factor (TNF)-alpha and IL-17. Our study was aimed at evaluating the early effect of IL-22 alone or in combination with TNF-alpha and IL-17 by immunofluorescence on i) keratinocyte (KC) proliferation, ii) terminal differentiation biomarkers as keratin (K) 10 and 17 expression, iii) intercellular junctions. Transmission electron microscopy (TEM) analysis was performed. A model of human skin culture reproducing a psoriatic microenvironment was used. Plastic surgery explants were obtained from healthy young women (n=7) after informed consent. Fragments were divided before adding IL-22 or a combination of the three cytokines, and harvested 24 (T24), 48 (T48), and 72 (T72)h later. From T24, in IL-22 samples we detected a progressive decrease in K10 immunostaining in the spinous layer paralleled by K17 induction. By TEM, after IL-22 incubation, keratin aggregates were evident in the perinuclear area. Occludin immunostaining was not homogeneously distributed. Conversely, KC proliferation was not inhibited by IL-22 alone, but only by the combination of cytokines. Our results suggest that IL-22 affects keratinocyte terminal differentiation, whereas, in order to induce a proliferation impairment, a more complex psoriatic-like microenvironment is needed.
摘要：
白细胞介素（IL）-22是一种促炎细胞因子，与其他细胞因子一起驱动银屑病病变的进展，肿瘤坏死因子（TNF）-α和IL-17。我们的研究旨在通过免疫荧光评估IL-22单独或与TNF-α和IL-17联合对i）角质形成细胞（KC）增殖的早期作用，ii)终末分化生物标志物如角蛋白(K)10和17表达，iii)细胞间连接。进行透射电子显微镜(TEM)分析。使用了复制牛皮癣微环境的人类皮肤培养模型。在知情同意后，从健康的年轻女性（n=7）获得整形手术外植体。在添加IL-22或三种细胞因子的组合之前，将片段分开，收获24（T24），48(T48),和72（T72）h后。从T24开始，在IL-22样品中，我们检测到棘层中K10免疫染色的逐渐降低与K17诱导平行。通过TEM，IL-22孵育后，角蛋白聚集体在核周区域很明显。Occludin免疫染色不均匀分布。相反，KC增殖不被单独的IL-22抑制,但只能通过细胞因子的组合。我们的结果表明，IL-22影响角质形成细胞的终末分化，然而,为了诱导增殖受损，需要一个更复杂的牛皮癣样的微环境。
