Runx3对寻常性银屑病患者Th17/Treg细胞分化的影响及其作用机制

Effect of Runx3 on Th17/Treg Cells Differentiation in Psoriasis and the Underlying Mechanism

目的探讨Runx3对银屑病患者Th17,Treg细胞分化的影响及作用机制。方法收集58例银屑病患者和50例健康对照者血液样本,应用密度梯度离心法分离外周血CD4^+T细胞,qRT-PCR检测Runx3的mRNA水平;采用RNA干扰法下调Runx3的表达水平,流式细胞仪检测Th17和Treg细胞水平;ELISA法测定外周血IL-17,IL-23,TGF-β,IL-10含量;实时定量PCR法检测RORγt,Foxp3的mRNA水平。结果与对照组相比,银屑病患者外周血CD4^+T细胞中Runx3的表达明显升高。Runx3-siRNA转染后,Th17/Treg细胞比值降低,同时伴随有Th17型炎性因子IL-17,IL-23表达下降以及Treg型抗炎因子TGF-β,IL-10的上调。机制分析证实,Runx3沉默后,细胞中Th17转录因子RORγt明显下降,而Treg转录调节因子Foxp3水平增加。结论 Runx3可通过RORγt,Foxp3调控CD4^+T细胞向Th17,Treg型细胞的分化,影响银屑病患者Th17/Treg比例的失衡,提示其可作为银屑病防治的新方向。

Objective To investigate the function and the underlying mechanism of Runx3 on Th17 and Treg cells differentiate in psoriasis. Methods Fifty eight patients with psoriasis vulgaris and 50 healthy controls were enrolled in our study and their peripheral blood samples were obtained. CD4 ＋ T cells in the peripheral blood samples were isolated by density gradient centrifugation. The mRNA levels of Runx3 in CD4 ＋ T cells were analyzed by qRT-PCR. After silencing the expression of Runx3 by its specific siRNA, flow cytometry was performed to determine the percentage of Th17 and Treg cell. The secretions of IL-17, IL-23 ,TGF-β, IL-10 were analyzed by ELISA. Furthermore, the mRNA levels of RORγt, Foxp3 were determined by qRT-PCR. Results The expressions of Runx3 in peripheral blood CD4 ＋ T cells were significantly increased in patients with psoriasis compared with the control groups. Additionally, Runx3 knockdown significantly decreased the ratio of Th17/Treg cells. Furthermore, Runx3 knockdown down-regulated the expression of IL-17 and IL-23, but up-regnlated TGF-β and IL-10 expression. The mechanism investigation revealed that Runnx3 knockdown significantly inhibited the expression of ThlT-specific transcription factor RORγt, while promoted the level of Treg-specific transcription factor Foxp3. Conclusion Runx3 may affect the imbalance of Th17/Treg levels in patients with psoriasis by regulating their specific transcription factor RORγt and Foxp3, suggesting a potential target for prevention and treatment of psoriasis.