STAT1和T-bet基因敲除在咪喹莫特诱导的小鼠银屑病模型中的不同作用

Differential roles of STAT1 and T-bet in imiquimod-induced psoriasiform skin inflammation

目的观察STAT1信号分子和T-bet转录因子在咪喹莫特诱导的银屑病疾病模型中的不同作用。方法将雄性8周龄129和C57BL/6小鼠分别随机分为正常对照组、野生型咪喹莫特诱导组,将雄性8周龄STAT1-/-小鼠和T-bet-/-小鼠分为STAT1-/-咪喹莫特诱导组、T-bet-/-咪喹莫特诱导组,依据PASI评分标准记录评价小鼠银屑病疾病模型的严重程度,HE染色观察疾病模型中皮损组织的形态和炎性细胞浸润情况来评价其病理学改变,实时荧光定量PCR检测疾病模型的皮损组织中相关细胞因子基因表达水平的改变。结果局部给予咪喹莫特诱导后4种小鼠(129、C57BL/6、STAT1-/-、T-bet-/-)背部皮肤均出现不同程度红斑、鳞屑、炎症细胞浸润。与T-bet-/-对比,STAT1-/-给药组皮炎反应更严重。与野生型给药组相比,STAT1-/-给药组分泌的IL-22水平明显升高而IL-17升高不明显。结论 STAT1信号分子可能通过除Th17细胞分泌外的其他途径调控IL-22表达水平,从而影响银屑病严重程度。

Psoriasis is a common chronic inflammatory skin disease characterized by abnormal keratinocyte differentiation and proliferation, as well as abnormal activated T cells infiltration. Recent studies have demonstrated that Th17 family cytokine IL-22 plays a critical role in the pathogenesis of psoriasis, and may serve as a novel therapeutic target. In this study, we use STAT1 and T-bet knock-out mice to evaluate the roles of STAT1 and T-bet in an imiquimod-induced psoriatic model. Mice were topically treated with imiquimod to trigger psoriasiform skin inflammation. Comparing to T-bet knock-out mice, STAT1 knock-out mice showed significantly higher levels of IL-22 expression and much severer skin inflammation, despite of lower levels of IL-17 expression. STAT1 deficiency had little effects on IL-17 expression compared to wild type animals. Our results demonstrated that STAT1 plays key roles in regulating IL-22 expression and psoriasis disease pathogenesis.