IL-17E (IL-25) and IL-17A Differentially Affect the Functions of Human Keratinocytes
IL-17E (IL-25) and IL-17A Differentially Affect the Functions of Human Keratinocytes
复制标题
DOI：
10.1016/j.jid.2019.12.013
复制
发表时间：
2020-07-01
影响因子：
6.5
通讯作者：
Brembilla, Nicolo Costantino
中科院分区：
文献类型：
--
作者：
Borowczyk, Julia;Buerger, Claudia;Brembilla, Nicolo Costantino
我们的小组最近表明，角质形成细胞衍生的IL-17 E（IL-25），IL-17家族的六个成员之一，在银屑病皮损中过表达，并参与其病理生理学。我们在这里表明，IL-22增强IL-17 E在人角质形成细胞的生产，这些细胞在其表面展示一个完整的IL-17 E受体，其表达进一步诱导IL-17 A，表明IL-17 E的潜在自分泌效应。因此，我们研究了IL-17 E对人原代角质形成细胞功能的影响。IL-17 E促进二维和三维培养物中角质形成细胞的增殖，并引起分化相关基因转录物（例如，角蛋白10），而它们的表达被IL-17 A抑制或不改变。与IL-17 A相反，IL-17 E不参与抗菌蛋白的诱导。对细胞运动的时间推移分析表明，IL-17 E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。在IL-17 A刺激后未观察到此类作用。总之，我们鉴定了IL-17 E的作用明显不同于IL-17 A，指出IL-17 E在表皮的生理学和病理生理学中的重要作用。
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.