Suppression of IL-17A-induced CCL20 production by cytokine inducible SH2-containing protein 1 in epidermal keratinocytes
Suppression of IL-17A-induced CCL20 production by cytokine inducible SH2-containing protein 1 in epidermal keratinocytes
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DOI：
10.1016/j.jdermsci.2021.01.005
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发表时间：
2021-03-01
影响因子：
4.6
通讯作者：
Sayama, Koji
中科院分区：
文献类型：
--
作者：
Tohyama, Mikiko;Matsumoto, Akira;Sayama, Koji
背景：特应性皮炎皮损比银屑病皮损Th 17细胞少，导致皮肤感染频繁。CCL 20是一种对募集Th 17细胞很重要的趋化因子，其表达在特应性皮炎的病变中受到抑制。我们以前报道，IL-4诱导的表达的姜黄素诱导SH 2-containing蛋白1（CIS 1），CIS/SOCS家族的成员，在表皮keratinocyte.Objective：研究是否CIS 1影响CCL 20的生产在表皮keratinocyte.Methods：CIS 1的表达进行了检查在特应性皮炎皮肤和培养的角质形成细胞。CIS 1过表达对IL-17 A产生CCL 20的影响，以及CIS 1抑制的信号通路，在体外进行了评估。当使用腺病毒载体在角质形成细胞中表达CIS 1时，IL-17 A诱导的CCL 20表达而不是HBD 2或S100 A7表达被显著抑制。CIS 1不改变TNF-α/IL-1诱导的CCL 20产生。CIS 1的过表达减弱IL-17 A诱导的ERK磷酸化。ERK磷酸化由Act 1和Src家族激酶途径介导。CIS 1过表达抑制Src磷酸化。在Src家族激酶中，Yes激酶可能起着重要作用，因为IL-17 A可通过抑制表皮角质形成细胞中Yes的表达，抑制ERK的磷酸化和CCL 20 mRNA的表达。结论：Th 2型细胞因子诱导的CIS 1可通过抑制Src家族激酶而改变表皮角质形成细胞对IL-17 A的反应。(C)2021由Elsevier B. V.代表日本皮肤病研究学会出版。
Background: Lesions of atopic dermatitis have fewer Th17 cells than those of psoriasis, resulting in frequent skin infections. Expression of CCL20, a chemokine that is important for recruiting Th17 cells, is suppressed in the lesions of atopic dermatitis. We previously reported that IL-4 induces the expression of cytokine-inducible SH2-containing protein 1 (CIS1), a member of the CIS/SOCS family, in epidermal keratinocytes.Objective: To investigate whether CIS1 influences CCL20 production in epidermal keratinocytes.Methods: Expression of CIS1 was examined in atopic dermatitis skin and in cultured keratinocytes. The effects of overexpression of CIS1 on CCL20 production by IL-17A, and on signaling pathways inhibited by CIS1, were assessed in vitro.Results: Expression of CIS1 was enhanced in the basal layer of the lesional epidermis of skin with atopic dermatitis. When CIS1 was expressed in keratinocytes using adenoviral vectors, IL-17A-induced CCL20 expression, but not HBD2 or S100A7 expression, was significantly suppressed. TNF-alpha/IL-1-induced CCL20 production was not altered by CIS1. Overexpression of CIS1 attenuated IL-17A-induced ERK phosphorylation. ERK phosphorylation was mediated by the Act1 and Src family kinase pathways. CIS1 overexpression suppressed Src phosphorylation. Among the Src family kinases, the Yes kinase may have an important role because knockdown of Yes in epidermal keratinocytes resulted in suppression of ERK phosphorylation and CCL20 mRNA expression by IL-17A.Conclusion: CIS1 induced by Th2 cytokines has the ability to change the response of epidermal keratinocytes to IL-17A by suppression of Src family kinases. (C) 2021 Published by Elsevier B.V. on behalf of Japanese Society for Investigative Dermatology.