IL-17 cytokines, in particular IL-17A, are critical effectors in psoriasis. Antibodies that block IL-17A are highly efficacious in treating psoriasis. Likewise, disruption of IL-17 cytokines signaling, such as via the loss of the adaptor CIKS/Act1, ameliorates inflammation in mouse models of psoriasis. IL-17A promotes a cascade of effects, including the robust production of IL-19 in both humans and mice. IL-19, along with IL-20 and IL-24, signal via IL-20 receptors and comprise a subgroup within the IL-10 cytokine family. The role of these three cytokines in psoriasis is unresolved. They have been linked to inflammatory processes, including psoriatic pathology, but these cytokines have also been reported to suppress inflammation in other contexts. In this study, we demonstrate that signaling via IL-20 receptors, including in response to IL-19, delimited aspects of imiquimod-induced psoriatic inflammation. IL-20 receptor signaling suppressed the dermal production of the CCL2 chemokine and thereby reduced CCL-2-driven infiltration of inflammatory cells into the dermis, including IL-17A-producing γδT cells. This constitutes a negative feedback, since IL-17A strongly induces IL-19 in keratinocytes. The effects of IL-17 cytokines in this inflammatory setting are dynamic; they are central to the development of both dermal and epidermal hallmarks of psoriasis but also initiate a path to mitigate inflammatory damage.

中文翻译：

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IL-20受体信号传导限制了银屑病炎症中IL-17的产生。

IL-17细胞因子，尤其是IL-17A，是牛皮癣的关键效应物。阻断IL-17A的抗体在治疗牛皮癣方面非常有效。同样，IL-17细胞因子信号转导的破坏（例如通过衔接子CIKS / Act1的丧失）可改善银屑病小鼠模型的炎症。IL-17A促进一连串的作用，包括在人和小鼠中强劲产生IL-19。IL-19与IL-20和IL-24一起通过IL-20受体发出信号，并构成IL-10细胞因子家族中的一个亚组。这三种细胞因子在牛皮癣中的作用尚未阐明。它们与包括牛皮癣病理在内的炎症过程有关，但是据报道，这些细胞因子还可以在其他情况下抑制炎症。在这项研究中，我们证明了通过IL-20受体的信号传导，包括对IL-19的响应，限定了咪喹莫特诱发的牛皮癣炎症的各个方面。IL-20受体信号传导抑制了CCL2趋化因子的真皮产生，从而减少了CCL-2驱动的炎症细胞向真皮的渗透，包括产生IL-17A的γδT细胞。这构成了负面反馈，因为IL-17A在角质形成细胞中强烈诱导IL-19。IL-17细胞因子在这种炎症环境中的作用是动态的。它们对于牛皮癣的皮肤和表皮标志的发展至关重要，但也为减轻炎症性损伤开辟了道路。这构成了负面反馈，因为IL-17A在角质形成细胞中强烈诱导IL-19。IL-17细胞因子在这种炎症环境中的作用是动态的。它们对于牛皮癣的皮肤和表皮标志的发展至关重要，但也为减轻炎症性损伤开辟了道路。这构成了负面反馈，因为IL-17A在角质形成细胞中强烈诱导IL-19。IL-17细胞因子在这种炎症环境中的作用是动态的。它们对于牛皮癣的皮肤和表皮标志的发展至关重要，但也为减轻炎症性损伤开辟了道路。