Department of Dermatology, Binzhou Medical University Hospital, 661 Second Huanghe Road, Binzhou 256603, China.
Department of Endocrinology and Metabolism, Binzhou Medical University Hospital, 661 Second Huanghe Road, Binzhou 256603, China.
Mediators Inflamm. 2018 Mar 4;2018:3069521. doi: 10.1155/2018/3069521. eCollection 2018.
To evaluate the regulating effect of Notch1 signaling on Th17/Treg immune imbalance in psoriasis vulgaris (PV).
Notch1, Hes-1, RORt, Foxp3, IL-17, and IL-10 mRNA expression, as well as Th17 and Treg cell percentages in peripheral CD4 T cells, were detected by real-time quantitative RT-PCR and flow cytometry, and serum concentrations of IL-17 and IL-10 were detected by ELISA in 36 PV patients and 32 healthy controls. Additionally, CD4 T cells from 12 PV patients were treated with -secretase inhibitor DAPT, and the above indexes were measured.
PV patients presented distinct Th17/Treg immune imbalance and highly expressed Notch1 and Hes-1 mRNA levels, which were positively correlated with psoriasis area and severity index (PASI) and the ratios of Th17/Treg and RORt/Foxp3. DAPT treatment resulted in the obvious downregulation of Th17 cell percentage in cocultured CD4 T cells, RORt and IL-17 mRNA levels, and IL-17 concentration in cell-free supernatant from cocultured CD4 T cells of PV patients in a dose-dependent manner, while there was no significant influence on Treg cell percentage, Foxp3, and IL-10 expression, therefore leading to the recovery of Th17/Treg immune imbalance.
Notch1 signaling may contribute to the pathogenesis of PV by regulating Th17/Treg immune imbalance.
评估 Notch1 信号对寻常型银屑病（PV）中 Th17/Treg 免疫失衡的调节作用。
采用实时定量 RT-PCR 和流式细胞术检测 Notch1、Hes-1、RORt、Foxp3、IL-17 和 IL-10mRNA 的表达，以及外周血 CD4 T 细胞中 Th17 和 Treg 细胞的百分比；采用 ELISA 法检测 36 例 PV 患者和 32 例健康对照者血清中 IL-17 和 IL-10 的浓度。此外，用β-分泌酶抑制剂 DAPT 处理 12 例 PV 患者的 CD4 T 细胞，检测上述指标。
PV 患者存在明显的 Th17/Treg 免疫失衡，Notch1 和 Hes-1mRNA 水平高表达，与银屑病面积和严重性指数（PASI）以及 Th17/Treg 和 RORt/Foxp3 比值呈正相关。DAPT 处理可明显下调共培养 CD4 T 细胞中 Th17 细胞百分比、RORt 和 IL-17mRNA 水平以及共培养 CD4 T 细胞无细胞上清液中 IL-17 浓度，呈剂量依赖性，而对 Treg 细胞百分比、Foxp3 和 IL-10 表达无明显影响，从而恢复 Th17/Treg 免疫失衡。
Notch1 信号可能通过调节 Th17/Treg 免疫失衡参与 PV 的发病机制。
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