Interleukin 17 Promotes Expression of Alarmins S100A8 and S100A9 During the Inflammatory Response of Keratinocytes.
Interleukin 17 Promotes Expression of Alarmins S100A8 and S100A9 During the Inflammatory Response of Keratinocytes.
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DOI：
10.3389/fimmu.2020.599947
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发表时间：
2020
影响因子：
7.3
通讯作者：
Roth J
中科院分区：
文献类型：
--
作者：
Christmann C;Zenker S;Martens L;Hübner J;Loser K;Vogl T;Roth J
牛皮癣是最常见的免疫介导的炎症性皮肤病之一。角化细胞中S100-alarmin家族的两种促炎分子S100A8和S100A9的表达和分泌是银屑病的标志，其特征还表现为角化细胞分化的改变。S100A8/S100A9（钙保护蛋白）二聚体与toll样受体4结合，在靶细胞中诱导炎症反应。靶向删除S100A9可减少小鼠牛皮癣样炎症的炎症表型。s100报警蛋白在角化细胞的分化和激活中起作用，但从未在原发性角化细胞中显示。我们现在证实，在吡喹莫德诱导的牛皮癣样皮肤炎症小鼠模型中，s100 -警报器的诱导与白细胞介素(IL)-1α、IL-6、IL- 17a或TNFα的表达增加有关。这种关联在银屑病患者的对照、病变和非病变皮肤的转录组数据中得到证实，并且在IL-17定向治疗后，S100-alarmin的表达下调。然而，通过分析原代S100A9−/−角质形成细胞，我们发现S100A8/S100A9的表达对角质形成细胞的成熟和炎症反应模式没有显著作用。此外，角质形成细胞不是S100A8/S100A9促炎作用的靶细胞。然而，不同的细胞因子，尤其是IL-17A和F，在银屑病中含量很高，在角化细胞成熟早期优先强烈诱导s100 -alarm的表达。我们的数据表明，S100A8和S100A9的表达并不主要影响角化细胞的成熟或激活，而是代表这些细胞在牛皮癣期间的炎症反应。
Psoriasis is one of the most common immune-mediated inflammatory skin diseases. Expression and secretion of two pro-inflammatory molecules of the S100-alarmin family, S100A8 and S100A9, in keratinocytes is a hallmark of psoriasis, which is also characterized by an altered differentiation of keratinocytes. Dimers of S100A8/S100A9 (calprotectin) bind to Toll-like receptor 4 and induce an inflammatory response in target cells. Targeted deletion of S100A9 reduced the inflammatory phenotype of psoriasis-like inflammation in mice. A role of S100-alarmins in differentiation and activation of keratinocytes was suggested but has been never shown in primary keratinocytes. We now confirm that induction of S100-alarmins in an imiquimod-induced murine model of psoriasis-like skin inflammation was associated with an increased expression of interleukin (IL)-1α, IL-6, IL-17A, or TNFα. This association was confirmed in transcriptome data obtained from controls, lesional and non-lesional skin of psoriasis patients, and a down-regulation of S100-alarmin expression after IL-17 directed therapy. However, analyzing primary S100A9−/− keratinocytes we found that expression of S100A8/S100A9 has no significant role for the maturation and inflammatory response pattern of keratinocytes. Moreover, keratinocytes are no target cells for the pro-inflammatory effects of S100A8/S100A9. However, different cytokines, especially IL-17A and F, highly abundant in psoriasis, strongly induced expression of S100-alarmins preferentially during early maturation stages of keratinocytes. Our data indicate that expression of S100A8 and S100A9 does not primarily influence maturation or activation of keratinocytes but rather represents the inflammatory response of these cells during psoriasis.
影响因子：
3.7
作者：
Scholz T;Weigert A;Brüne B;Sadik CD;Böhm B;Burkhardt H
通讯作者：
Burkhardt H