Department of Rheumatology and Immunology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China.
Department of Communication Sciences & Disorders, MGH Institute of Health Professions, Boston, Massachusetts, USA.
Clin Transl Med. 2024 Sep;14(9):e1800. doi: 10.1002/ctm2.1800.
To assess the impact of the IFIT3/TBK1 signalling pathway in activating plasmacytoid dendritic cells (pDCs) and its role in the development of SSc.
Utilized single-cell RNA sequencing (scRNA-seq) and high-throughput transcriptome RNA sequencing to reveal the differential abundance of pDCs and the role of the key gene IFIT3 in SSc. Conducted in vitro cell experiments to evaluate the effect of IFIT3/TBK1 signalling pathway intervention on pDC activation cytokine release and fibroblast function. Constructed an IFIT3 mouse model using clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) gene editing to assess the potential benefits of intervening in the IFIT3/TBK1 signalling pathway on skin and lung fibrosis in the SSc mouse model.
The IFIT3/TBK1 signalling pathway plays a crucial role in activating pDCs, with IFIT3 acting as an upstream regulator of TBK1. Intervention in the IFIT3/TBK1 signalling pathway can inhibit pDC activation cytokine release and impact fibroblast function. The IFIT3 mouse model shows potential benefits of targeting the IFIT3/TBK1 signalling pathway in reducing skin and lung fibrosis in the SSc mouse model.
This study provides new insights into potential therapeutic targets for SSc, highlighting the critical role of the IFIT3/TBK1 signalling pathway in SSc development.
This study elucidates the pivotal role of plasmacytoid dendritic cells (pDCs) in systemic sclerosis (SSc). This study identified the key regulatory gene involved in systemic sclerosis (SSc) as IFIT3. This study has found that IFIT3 functions as an upstream regulatory factor, activating TBK1. This study provides Evidence of the regulatory effects of the IFIT3/TBK1 pathway on plasmacytoid dendritic cells (pDCs). This study validated the therapeutic potential using the IFIT3 mouse model.
评估 IFIT3/TBK1 信号通路在激活浆细胞样树突状细胞（pDC）中的作用及其在系统性硬化症（SSc）发病机制中的作用。
利用单细胞 RNA 测序（scRNA-seq）和高通量转录组 RNA 测序揭示 pDC 的差异丰度和关键基因 IFIT3 在 SSc 中的作用。进行体外细胞实验，评估 IFIT3/TBK1 信号通路干预对 pDC 激活细胞因子释放和成纤维细胞功能的影响。利用规律成簇间隔短回文重复（CRISPR）/CRISPR 相关蛋白 9（Cas9）基因编辑构建 IFIT3 小鼠模型，评估干预 IFIT3/TBK1 信号通路对 SSc 小鼠模型皮肤和肺纤维化的潜在益处。
IFIT3/TBK1 信号通路在激活 pDC 中起关键作用，IFIT3 作为 TBK1 的上游调节因子。干预 IFIT3/TBK1 信号通路可以抑制 pDC 激活细胞因子释放并影响成纤维细胞功能。IFIT3 小鼠模型显示出靶向 IFIT3/TBK1 信号通路在减少 SSc 小鼠模型皮肤和肺纤维化方面的潜在益处。
本研究为 SSc 的潜在治疗靶点提供了新的见解，强调了 IFIT3/TBK1 信号通路在 SSc 发病机制中的关键作用。
本研究阐明了浆细胞样树突状细胞（pDC）在系统性硬化症（SSc）中的关键作用。本研究确定了参与系统性硬化症（SSc）的关键调节基因是 IFIT3。本研究发现 IFIT3 作为上游调节因子，激活 TBK1。本研究提供了 IFIT3/TBK1 通路对浆细胞样树突状细胞（pDC）的调节作用的证据。本研究使用 IFIT3 小鼠模型验证了治疗潜力。
