Notch signaling pathway regulates IL-22 secretion by CD4+T cells in patients with Vogt-Koyanagi-Harada syndrome / 国际眼科杂志(Guoji Yanke Zazhi)

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.<p>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.<p>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.<p>CONCLUSION:Notch-AhR-IL-22 signaling pathway might take part in the pathogenesis of VKH syndrome.