Liu Baoyi, Xie Yongyi, Mei Xingyu, Sun Yue, Shi Weimin, Wu Zhouwei
Department of Dermatology, Shanghai General Hospital, Shanghai Jiaotong University, Shanghai 200080, P.R. China.
Department of Dermatology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, P.R. China.
Exp Ther Med. 2021 Feb;21(2):158. doi: 10.3892/etm.2020.9589. Epub 2020 Dec 17.
Previous studies have shown the participation of the cytokines interleukin (IL) 17A and IL22 in the development of vitiligo. The aryl hydrocarbon receptor (AhR) functions in the pathogenesis of vitiligo and can modulate cytokine production. The aim of the present study was to determine the relationship between AhR activation and the secretion of IL17A and IL22 in CD4 T cells in vitiligo. A total of 20 newly diagnosed patients with progressive, unstable vitiligo and 20 healthy controls were recruited. CD4 T cells and skin samples were collected. Immunohistochemistry, ELISA, reverse transcription-quantitative PCR, western blotting and RNA interference experiments were performed. The expression of AhR was significantly lower in the CD4 T cells and skin, both lesional and nonlesional, of patients with vitiligo compared with healthy subjects. AhR expression was markedly lower in nonlesional compared with lesional skin of patients with vitiligo. The expression levels of IL17A and IL22 were significantly higher in patients with vitiligo compared with healthy subjects. Knockdown of AhR significantly increased the production of IL17A and markedly decreased IL22 levels in the CD4 T cells of patients with vitiligo. extract EGb 761 activated AhR, inhibited IL17A secretion and enhanced IL22 release in the CD4 T cells of patients with vitiligo. In conclusion, reduced AhR expression is associated with progressive, unstable vitiligo. Activation of AhR with extract EGb 761 may have therapeutic potential for decreasing IL17A levels and increasing IL22 levels in patients with vitiligo.
先前的研究表明细胞因子白细胞介素（IL）-17A和IL-22参与了白癜风的发病过程。芳烃受体（AhR）在白癜风的发病机制中发挥作用，并可调节细胞因子的产生。本研究的目的是确定AhR激活与白癜风患者CD4⁺ T细胞中IL-17A和IL-22分泌之间的关系。共招募了20例新诊断的进展期、不稳定型白癜风患者和20名健康对照者。采集了CD4⁺ T细胞和皮肤样本。进行了免疫组织化学、酶联免疫吸附测定（ELISA）、逆转录定量聚合酶链反应（RT-qPCR）、蛋白质免疫印迹法和RNA干扰实验。与健康受试者相比，白癜风患者的CD4⁺ T细胞以及皮损和非皮损皮肤中AhR的表达均显著降低。与白癜风患者的皮损皮肤相比，非皮损皮肤中AhR的表达明显更低。与健康受试者相比，白癜风患者中IL-17A和IL-22的表达水平显著更高。敲低AhR可显著增加白癜风患者CD4⁺ T细胞中IL-17A的产生，并显著降低IL-22水平。银杏叶提取物EGb 761激活AhR，抑制白癜风患者CD4⁺ T细胞中IL-17A的分泌，并增强IL-22的释放。总之，AhR表达降低与进展期、不稳定型白癜风有关。用银杏叶提取物EGb 761激活AhR可能对降低白癜风患者的IL-17A水平和提高IL-22水平具有治疗潜力。
