利用基因敲除小鼠研究咪喹莫特诱导银屑病模型中转录因子RORγt的作用

Analysis of the roles of RORγt in imiquimod-induced psoriasiform skin inflammation using knockout mice

目的观察RORγt转录因子在咪喹莫特诱导的小鼠银屑病模型中的作用。方法雌性8周C57BL/6小鼠随机分为正常对照组、野生型给药组、RORγt-/-给药组,用PASI评分观察小鼠模型皮损的变化,HE染色观察皮损组织形态学变化,实时荧光定量PCR对小鼠皮损组织中的细胞因子mRNA相对表达量进行检测。结果局部给予咪喹莫特后野生型小鼠背部皮肤出现红斑、鳞屑、增厚典型银屑病样皮损,RORγt-/-给药组小鼠症状明显减轻。RORγt-/-组IL-22、IL-17、IL-23细胞因子的相对表达量明显低于野生型给药组。结论 RORγt转录因子调控Th17细胞因子IL-22、IL-17表达和该模型疾病的病理进程。

Psoriasis is a common relapsing chronic autoimmune skin disease characterized by erythematous scaly plaques. The Th17-related cytokines are functionally implicated in the psoriatic pathology and the transcription factor RORγt is critical for regulating the expression of Th17-related cytokines in vitro. In this study, we used RORγt knock-out mice to evaluate the roles of RORγt in imiquimod-induced psoriasiform skin inflammation. Mice were topically treated with imiquimod to trigger the psoriasiform skin inflammation. As compared with wild-type mice, RORγt knock-out mice demonstrated lighter scaly skin lesions and dramatic decrease in acanthosis at macroscopic level after imiquimod induction. Furthermore, the expression of ThlT-related cytokines was decreased significantly in the RORγt knock-out mice. Our data demonstrated that the transcription factor RORγt plays key roles in regulating ThlT-related cytokines and psoriasis disease pathogenesis.