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[摘要]
目的：观察Notch受体和IL-22在Vogt-小柳原田(VKH)综合征患者中的表达变化，探讨Notch信号通路对VKH综合征患者CD4+T细胞分泌IL-22的调控作用。
方法：选取VKH综合征患者35例(活动期15例和静止期20例)和健康对照者12例，分选血浆和CD4+T细胞，qRT-PCR和Western blot法检测Notch受体，ELISA法检测血浆IL-22表达，流式细胞术检测Th17和Th22的比例。观察抑制Notch信号通路对VKH综合征患者CD4+T细胞转录因子相对表达量和IL-22分泌水平的变化。
结果：活动期VKH综合征患者CD4+T细胞中Notch1～3较静止期和健康对照者显著升高。活动期VKH综合征患者血浆IL-22及Th17、Th22水平高于静止期和健康对照者。抑制Notch信号通路可导致活动性VKH综合征患者CD4+T细胞中AhR mRNA降低，分泌IL-22水平降低。
结论：Notch-AhR-IL-22信号通路可能参与了VKH综合征的发病。
[Key word]
[Abstract]
AIM:To investigate the changes of Notch receptors and interleukin(IL)-22 expression in patients with Vogt-Koyanagi-Harada(VKH)syndrome, and to assess the regulatory activity of Notch signaling to IL-22 production by CD4
+ T cells in patients with VKH syndrome.
METHODS: Thirty-five patients with VKH syndrome(including fifteen active VKH and twenty inactive VKH)and twelve healthy controls were enrolled. Plasma was isolated, and CD4+T cells were purified. Notch receptors were investigated by qRT-PCR and Western blot. Plasma IL-22 expression was measured by ELISA. The percentage of Th17 and Th22 cells was investigated by flow cytometry. CD4+T cells, which were purified from active VKH patients, were stimulated with Notch signaling inhibitor DAPT. mRNA expression of transcription factor in CD4+T cells as well as IL-22 secretion by CD4+T cells was investigated.
RESULTS: Notch1-Notch3 in CD4+T cells from active VKH syndrome patients was significantly elevated in comparison with inactive VKH and healthy controls. Plasma IL-22 expression and percentage of Th17 and Th22 was notably increased in active VKH syndrome in comparison with inactive VKH and controls. DAPT stimulation inhibited Notch signaling pathway in CD4+T cells, leading to the down-regulation of AhR mRNA and IL-22 secretion.
CONCLUSION:Notch-AhR-IL-22 signaling pathway might take part in the pathogenesis of VKH syndrome.
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