靶向树突状细胞中的 STING 可抑制 IL-17A 的产生,从而缓解银屑病炎症。

IF 21.8 1区 医学 Q1 IMMUNOLOGY
Xiaoying Sun, Liu Liu, Jiao Wang, Xiaorong Luo, Meng Wang, Chunxiao Wang, Jiale Chen, Yaqiong Zhou, Hang Yin, Yuanbin Song, Yuanyan Xiong, Hongjin Li, Meiling Zhang, Bo Zhu, Xin Li
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引用次数: 0

摘要

银屑病是一种常见的慢性炎症性皮肤病,由树突状细胞(DC)和 T 细胞的异常活化驱动,最终导致白细胞介素(IL)-23 和 IL-17A 等细胞因子的产生增加。目前已确定 cGAS-STING 通路对银屑病炎症至关重要,但 cGAS-STING 信号在 DC 中的具体作用仍不清楚。在本研究中,我们通过分析临床患者和咪喹莫特(IMQ)处理过的小鼠样本,证实了 cGAS-STING 信号在银屑病皮损中的上调。利用条件性Sting基因敲除转基因小鼠模型,我们阐明了DC中的cGAS-STING信号对银屑病炎症中IL-17和IFN-γ产生的T细胞激活的影响。消减Sting阻碍了DC的活化,导致产生IL-17的T细胞和Th1细胞数量减少,从而减轻了IMQ诱导的小鼠模型中的银屑病炎症。此外,我们还探索了 STING 抑制剂 C-176 的治疗潜力,它能减轻银屑病炎症并增强抗 IL-17A 治疗反应。我们的研究结果强调了 DCs 中的 cGAS-STING 信号在驱动银屑病炎症中的关键作用,并凸显了治疗银屑病的前景。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Targeting STING in dendritic cells alleviates psoriatic inflammation by suppressing IL-17A production

Targeting STING in dendritic cells alleviates psoriatic inflammation by suppressing IL-17A production

Targeting STING in dendritic cells alleviates psoriatic inflammation by suppressing IL-17A production
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.
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来源期刊
CiteScore
31.20
自引率
1.20%
发文量
903
审稿时长
1 months
期刊介绍: Cellular & Molecular Immunology, a monthly journal from the Chinese Society of Immunology and the University of Science and Technology of China, serves as a comprehensive platform covering both basic immunology research and clinical applications. The journal publishes a variety of article types, including Articles, Review Articles, Mini Reviews, and Short Communications, focusing on diverse aspects of cellular and molecular immunology.
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