Notch1信号通路调控银屑病模型小鼠Th17细胞分化和功能

发布时间：2018-03-09 00:27

  本文选题：银屑病　切入点：Notch　出处：《中国免疫学杂志》2017年07期 　论文类型：期刊论文

【摘要】：目的:探讨Notch1信号通路对银屑病模型小鼠Th17细胞分化和功能的调控作用。方法:以5%咪喹莫特外涂联合α-2b干扰素腹腔注射的方法制备20只银屑病模型小鼠,免疫磁珠分离小鼠脾脏CD4~+T淋巴细胞,流式细胞术检测Th17细胞比例,实时荧光定量RT-PCR检测Th17细胞特异性转录因子RORγt、效应性细胞因子IL-17A、Notch1信号分子及其靶基因Hes-1的mRNA表达水平,并与10只对照组小鼠相比较。将银屑病模型小鼠CD4~+T淋巴细胞分为未干预对照组和Notch1抑制剂组(γ-分泌酶抑制剂DAPT),检测DAPT阻断Notch1信号对银屑病模型小鼠Notch1信号分子及Hes-1、Th17细胞比例、RORγt及IL-17A表达水平的影响。结果:银屑病模型小鼠CD4~+T淋巴细胞中Th17细胞比例,RORγt、IL-17A、Notch1及Hes-1的mRNA表达水平均显著高于对照小鼠[分别为(2.97±0.86)%比(0.65±0.11)%,t=15.083;(5.75±0.61)比(1.57±0.43),t=21.630;(7.83±0.97)比(1.63±0.31),t=25.348;(7.10±1.37)比(1.47±0.34),t=17.386;(7.30±1.15)比(1.67±0.48),t=18.840,P均0.01];与未干预对照组相比,银屑病模型小鼠CD4~+T淋巴细胞各DAPT处理组中Notch1、Hes-1mRNA表达水平,Th17细胞比例、RORγt与IL-17A mRNA表达水平及培养上清液中IL-17A含量均明显下降,组间比较差异具有统计学意义(F值分别为74.368、89.719、126.572、94.558、124.323和123.231,P均0.01),且随DAPT浓度的增加呈剂量依赖性降低。结论:Notch1信号通路能够调控银屑病模型小鼠Th17细胞的分化和功能,对银屑病的免疫靶向治疗有潜在价值。
[Abstract]:Objective: to investigate the effects of Notch1 signaling pathway on the differentiation and function of Th17 cells in psoriatic model mice. Methods: twenty psoriatic model mice were induced by 5% imiquimod plus 伪 -2b interferon intraperitoneal injection. CD4 ~ T lymphocytes were isolated from mouse spleen by immunomagnetic beads, the proportion of Th17 cells was detected by flow cytometry, the mRNA expression levels of Th17 cell specific transcription factor ROR 纬 t, effector cytokine IL-17Atch1 signal molecule and its target gene Hes-1 were detected by real-time fluorescence quantitative RT-PCR. The CD4T lymphocytes of psoriatic model mice were divided into control group and Notch1 inhibitor group (Notch1 inhibitor DAPT). The effect of DAPT blocking Notch1 signal on Notch1 signal was detected in psoriatic model mice. The expression of ROR 纬 t and IL-17A in CD4 ~ T lymphocytes of psoriatic model mice was significantly higher than that in control mice (2.97 卤0.86% vs 0.65 卤0.113 卤0.61), respectively. Results: the ratio of Th17 cells in CD4T lymphocytes of psoriatic mice was significantly higher than that in control mice (1.63 卤0.31), 25.348 ~ (7.10 卤1.3710) vs 1.47 卤0.34 ~ (17.6)% vs 7.30 卤1.15 (respectively). The expression of ROR 纬 t in psoriatic mice was higher than that in control mice (2.97 卤0.86% vs 0.65 卤0.11) and 1.57 卤0.43 ~ T (21.6307.83 卤0.97) vs 1.63 卤0.31 (7.10 卤1.3710) vs 1.47 卤0.34 (7.30 卤1.15)). Compared with the control group without intervention, there was no significant difference between the two groups (1.67 卤0.48) and 18.840 (P 0.01). The expression level of Notch1Hes-1mRNA in CD4T lymphocytes of psoriatic mice and the ratio of Th17 cells to ROR 纬 t and IL-17A mRNA, and the content of IL-17A in culture supernatant were significantly decreased. The difference between the two groups was statistically significant (74.368,89.719) 126.57294.558 (124.323) and 123.231 (P) 0.01g, respectively, and decreased in a dose-dependent manner with the increase of DAPT concentration. Conclusion the DAPT signaling pathway can regulate the differentiation and function of Th17 cells in psoriatic model mice. Immune targeting therapy for psoriasis has potential value.
【作者单位】： 滨州医学院附属医院;
【基金】：山东省医药卫生科技发展计划项目(2016WS0045)资助
【分类号】：R-332;R758.63

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