Our group has recently shown that keratinocyte-derived IL-17E (IL-25), one of six members of the IL-17 family, is overexpressed in lesional psoriatic skin and is involved in its pathophysiology. We show here that IL-22 enhances IL-17E production in human keratinocytes and that these cells display a complete IL-17E receptor at their surface, the expression of which is further induced by IL-17A, indicating a potential autocrine effect of IL-17E. Therefore, we addressed the impact of IL-17E on the function of human primary keratinocytes. IL-17E promoted the proliferation of keratinocytes in two-dimensional and three-dimensional cultures and caused the concomitant upregulation of differentiation-associated gene transcripts (e.g., keratin 10), whereas their expression was either inhibited or not changed by IL-17A. Contrary to IL-17A, IL-17E was not involved in the induction of antimicrobial proteins. Time-lapse analysis of cell movement showed that IL-17E influences cell motility, increasing both cell speed and displacement. This was associated with specific changes in the actin cytoskeleton organization and the cell-substrate adhesion. No such effects were observed upon IL-17A stimulation. In summary, we identified effects of IL-17E clearly distinct from IL-17A, pointing toward an important role of IL-17E in the physiology and pathophysiology of the epidermis.

我们的小组最近表明，角质形成细胞衍生的IL-17E（IL-25）是IL-17家族的六种成员之一，在皮损皮损皮肤中过表达，并参与其病理生理。我们在此处显示IL-22增强人角质形成细胞中IL-17E的产生，并且这些细胞在其表面显示出完整的IL-17E受体，IL-17A进一步诱导其表达，表明IL-A的潜在自分泌作用17E。因此，我们解决了IL-17E对人原代角质形成细胞功能的影响。IL-17E在二维和三维培养中促进角质形成细胞的增殖，并导致分化相关基因转录本（例如，角蛋白10）的上调，而IL-17A抑制或不改变其表达。与IL-17A相反，IL-17E不参与抗微生物蛋白的诱导。细胞运动的时移分析表明，IL-17E影响细胞运动，增加细胞速度和位移。这与肌动蛋白细胞骨架组织和细胞-基质粘附的特定变化有关。IL-17A刺激后未观察到此类影响。总之，我们确定了IL-17E的作用与IL-17A明显不同，这表明IL-17E在表皮的生理和病理生理中具有重要作用。IL-17A刺激后未观察到此类影响。总之，我们确定了IL-17E的作用与IL-17A明显不同，这表明IL-17E在表皮的生理和病理生理中起着重要的作用。IL-17A刺激后未观察到此类影响。总之，我们确定了IL-17E的作用与IL-17A明显不同，这表明IL-17E在表皮的生理和病理生理中起着重要的作用。