cGAS/STING信号通路在防治角膜移植免疫排斥中的作用机制研究

角膜盲是我国第二大致盲性眼病，多数可以通过角膜移植手术复明，但术后免疫排斥反应是移植失败的最主要原因。最新研究发现cGAS/STING信号通路通过活化抗原递呈细胞在抗感染、抗肿瘤以及自身免疫性疾病的致病中发挥关键作用。本团队在省科金资助下进行的前期研究结果显示：发生免疫排斥的角膜植片高表达cGAS/STING信号通路的关键蛋白，且其活性显著增强；cGAS/STING信号通路能促进抗原递呈细胞表达Ⅰ型干扰素和IL-1β的成熟。基于此，我们提出假说：cGAS/STING信号通路通过活化抗原递呈细胞启动角膜移植免疫排斥反应的病理过程。为验证此假说，我们拟采用小鼠角膜移植模型，结合体内外实验，探讨cGAS/STING信号通路对角膜移植免疫排斥反应的影响，并初步阐明该信号通路参与角膜移植免疫排斥的机制。通过本研究可以为临床防治角膜移植免疫排斥提供新的治疗靶点和理论依据。

Corneal blindness is the second most common blindness eye disease in China, most of which can be restored by keratoplasty, but corneal allograft rejection is the main cause for corneal transplantation failure. Recent studies have shown that cGAS/STING signaling pathway plays a key role in anti-infection, anti-cancer and pathogenesis of autoimmune diseases by activating antigen-presenting cells (APC). We found that the significantly elevated activity of cGAS/STING signaling in corneal allograft rejection; cGAS/STING signaling pathway in APC could not only promote the production of type I interferon, but also be involved in the maturation of IL-1β. Based on those observations, we propose that cGAS/STING signaling pathway contributes to the pathogenesis of corneal allograft rejection by activating APC. To verify this hypothesis, we will investigate the effect of cGAS/STING signaling pathway on corneal allograft rejection using mouse corneal transplantation model, and further explore the mechanism of cGAS/STING signaling pathway involved in the pathogenesis of corneal allograft rejection . This study will provide a new therapeutic target and theoretical basis for clinical prevention and treatment of corneal allograft rejection.