Institute for Immunology and School of Medicine, Tsinghua University, Beijing 100084, China; Tsinghua University-Peking University Joint Center for Life Sciences, Beijing 100084, China.
Institute for Immunology and School of Medicine, Tsinghua University, Beijing 100084, China.
Immunity. 2018 Apr 17;48(4):787-798.e4. doi: 10.1016/j.immuni.2018.03.019. Epub 2018 Apr 10.
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.
银屑病是一种慢性自身炎症性皮肤病。虽然来自淋巴细胞的白细胞介素-17（IL-17）已被证明在银屑病中起关键作用，但慢性皮肤炎症的发生和维持仍未得到很好的理解。白细胞介素-25（也称为 IL-17E）是另一种白细胞介素-17 家族细胞因子，其对过敏反应和 2 型免疫的调节作用已广为人知。在这里，我们已经表明，白细胞介素-25在银屑病患者的皮损皮肤中也高度表达，在咪喹莫特（IMQ）诱导的银屑病模型的鼠皮中受白细胞介素-17 调节。白细胞介素-25 注射可诱导皮肤炎症，而白细胞介素-25 的种系或角蛋白细胞特异性缺失可导致对 IMQ 诱导的银屑病产生抗性。通过角蛋白细胞中 IL-17RB 的表达，白细胞介素-25 通过激活 STAT3 转录因子刺激角蛋白细胞的增殖，并诱导炎症细胞因子和趋化因子的产生。因此，我们的数据表明，角蛋白细胞中的白细胞介素-17 诱导的自身调节回路是由白细胞介素-25 介导的，并表明该回路可作为治疗银屑病患者的靶点。
