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Abstract：
Psoriasis is a common chronic inflammatory skin disease driven by the aberrant activation of dendritic cells (DCs) and T cells, ultimately leading to increased production of cytokines such as interleukin (IL)-23 and IL-17A. It is established that the cGAS-STING pathway is essential for psoriatic inflammation, however, the specific role of cGAS-STING signaling in DCs within this context remains unclear. In this study, we demonstrated the upregulation of cGAS-STING signaling in psoriatic lesions by analyzing samples from both clinical patients and imiquimod (IMQ)-treated mice. Using a conditional Sting-knockout transgenic mouse model, we elucidated the impact of cGAS-STING signaling in DCs on the activation of IL-17- and IFN-γ-producing T cells in psoriatic inflammation. Ablation of the Sting hampers DC activation leads to decreased numbers of IL-17-producing T cells and Th1 cells, and thus subsequently attenuates psoriatic inflammation in the IMQ-induced mouse model. Furthermore, we explored the therapeutic potential of the STING inhibitor C-176, which reduces psoriatic inflammation and enhances the anti-IL-17A therapeutic response. Our results underscore the critical role of cGAS-STING signaling in DCs in driving psoriatic inflammation and highlight a promising psoriasis treatment.
摘要：
银屑病是由树突状细胞(DCs)和T细胞的异常激活引起的常见慢性炎症性皮肤病,最终导致细胞因子如白介素(IL)-23和IL-17A的产生增加。已确定cGAS-STING途径对银屑病炎症至关重要，然而,在这种情况下，cGAS-STING信号在DCs中的具体作用尚不清楚。在这项研究中,我们通过分析来自临床患者和咪喹莫特(IMQ)治疗小鼠的样本,证明了cGAS-STING信号在银屑病皮损中的上调.使用条件Sting敲除转基因小鼠模型，我们阐明了cGAS-STING信号在DC中对银屑病炎症中产生IL-17和IFN-γ的T细胞活化的影响。Sting的消融阻碍DC激活导致产生IL-17的T细胞和Th1细胞的数量减少，并因此随后在IMQ诱导的小鼠模型中减弱银屑病炎症。此外，我们探索了STING抑制剂C-176的治疗潜力,该抑制剂可减少银屑病炎症并增强抗IL-17A治疗反应.我们的结果强调了cGAS-STING信号在DC中驱动银屑病炎症的关键作用，并强调了有希望的银屑病治疗。
