清华董晨等:IL-25活化角化细胞促进银屑病

Immunity

4/10/18Article

22.845

影响因子

原标题:IL-25介导的角质细胞自调节回路在银屑病皮肤炎症中的重要作用

① IL-17在银屑病中起到关键作用,IL-17家族中的另一成员IL-25(又称IL-17E)在银屑病患者的病变皮肤中高表达,IL-25可调节过敏反应及2型免疫反应;② 在咪喹莫特(IMQ)诱导的银屑病小鼠模型的皮肤中,IL-25受到IL-17的调控;③ 注射IL-25可引起皮肤炎症,而germline或角化细胞特异性敲除IL-25可导致对小鼠产生对IMQ诱导银屑病的抗性;④ IL-25通过IL-17RB刺激角化细胞的增殖,并通过激活STAT3转录因子引起炎症细胞因子及趋化因子的产生。

银屑病 白介素-25(IL-25) 白介素-17(IL-17)

图片

Title:
An Interleukin-25-Mediated Autoregulatory Circuit in Keratinocytes Plays a Pivotal Role in Psoriatic Skin Inflammation

DOI:
10.1016/j.immuni.2018.03.019

Abstract & Authors展开

Abstract:
Psoriasis is a chronic autoinflammatory skin disease. Although interleukin-17, derived from lymphocytes, has been shown to be critical in psoriasis, the initiation and maintenance of chronic skin inflammation has not been well understood. IL-25 (also called IL-17E), another IL-17 family cytokine, is well known to regulate allergic responses and type 2 immunity. Here we have shown that IL-25, also highly expressed in the lesional skin of psoriasis patients, was regulated by IL-17 in murine skin of a imiquimod (IMQ)-induced psoriasis model. IL-25 injection induced skin inflammation, whereas germline or keratinocyte-specific deletion of IL-25 caused resistance to IMQ-induced psoriasis. Via IL-17RB expression in keratinocytes, IL-25 stimulated the proliferation of keratinocytes and induced the production of inflammatory cytokines and chemokines, via activation of the STAT3 transcription factor. Thus, our data demonstrate that an IL-17-induced autoregulatory circuit in keratinocytes is mediated by IL-25 and suggest that this circuit could be targeted in the treatment of psoriasis patients.

All Authors:
Miao Xu, Huiping Lu, Young-Hee Lee, Yelin Wu, Kewei Liu, Yuling Shi, Haoran An, Jingren Zhang, Xiaohu Wang, Yuping Lai, Chen Dong

First Authors:
Miao Xu

Correspondence:
Chen Dong

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