IL-23/STAT3信号通路是Th17细胞分化过程中的关键途径，Th17细胞异常被证实与自身免疫性疾病的发病密切相关。本课题组首次设计并制备了新型rhIL23R-CHR/Fc融和蛋白，通过拮抗内源性IL-23有效治疗自身免疫性疾病模型鼠。在深入研究融合蛋白作用机制时，我们发现Th17细胞关键转录因子RORγT的表达受lncRNA调节。因此，我们推测rhIL23R-CHR/Fc通过影响lncRNA来调控Th17细胞所导致的免疫失衡。本研究拟采用RNAi及CRISPR/Cas9技术，验证lncRNA调节Th17细胞的分化功能及对模型鼠治疗的影响；根据与其表达量密切相关的靶基因及信号通路，对lncRNA 发挥作用的分子机制进行探讨。本研究以rhIL23R-CHR/Fc发挥治疗作用为切入点，揭示lncRNA参与药效及调控下游基因的作用模式，为自身免疫性疾病预防、诊断和靶向治疗提供新的思路和策略。

IL-23/STAT3 signaling pathway is a key process to Th17 cell differentiation, and Th17 cells have been regarded closely related to the development of autoimmune diseases. We previously designed and prepared a new rhIL23R-CHR/Fc fusion protein for the first time to antagonize endogenous IL-23, which is effective in the treatment of experimental autoimmune encephalomyelitis model in mice. To futher elucidate the mechanism of action, we found that the key transcription factor RORγT in Th17 cells is regulated by lncRNA. Thus, we hypothesize that rhIL23R-CHR/Fc can regulate Th17 cells through lncRNA to balance the immune responses. In this proposal, we will use the techniques of RNAi and CRISPR/Cas9 to dissect the effects of lncRNA on Th17 cell differentiation and on the treatment of EAE model. Meanwhile, we will identify the target gene and its regulation mechanism. Differing from classic approaches to treat autoimmune disease and therapeutic strategies, rhIL23R-CHR/Fc might exert its curative effects through regulating the expression of lncRNA in addition to its function in downstream gene, which will offer new options for the treatment of autoimmune diseases.