Decreased IL-27 Expression in Association with an Increased Th17 Response in Vogt-Koyanagi-Harada Disease
Decreased IL-27 Expression in Association with an Increased Th17 Response in Vogt-Koyanagi-Harada Disease
复制标题
Vogt-小柳-原田病中 IL-27 表达减少与 Th17 反应增加相关
DOI：
10.1167/iovs.12-9863
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发表时间：
2012-07-01
影响因子：
4.4
通讯作者：
Yang, Peizeng
中科院分区：
文献类型：
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作者：
Wang, Chaokui;Tian, Yuan;Yang, Peizeng
目的. IL-27已成为动物模型中促炎性T细胞应答的重要调节剂。我们研究了IL-27在Vogt-Koyanagi-Harada（VKH）病中的病理生理作用。RT-PCR检测外周血单个核细胞（PBMCs）IL-27 P28和EBI 3 mRNA表达。采用ELISA法测定血清和外周血单个核细胞、初始CD 4（+）T细胞和DC-T共培养物上清中的细胞因子。流式细胞术用于评估产生IL-17的CD 4（+）T细胞的频率。活动期VKH患者外周血单个核细胞IL-27 P28 mRNA表达降低，外周血单个核细胞IL-27表达降低，外周血单个核细胞Th 17细胞表达升高。EBI 3 mRNA表达在各组间无差异。在Th 17极化条件下刺激初始CD 4（+）T细胞显示活动性VKH患者中Th 17细胞分化更高。IL-27显著抑制Th 17细胞分化。IL-27处理的DC显示出对Th 17分化的显著抑制。在活动性VKH患者中，通过IL-10测量的Tr 1细胞诱导存在显著缺陷。用皮质类固醇和环孢霉素A（CsA）治疗解决了与IL-27上调和IL-17下调相关的眼内炎症。体外实验表明，皮质类固醇可显著上调IL-27的表达，而CsA无此作用。目前的研究表明，IL-27的表达减少可能会导致更高的Th 17活动VKH患者，这可能会促进在这些患者中观察到的自身免疫反应。IL-27的操纵可能为治疗这种疾病提供新的靶点。（Invest Ophthalmol维斯科学。2012; 53：4668-4675）DOI：10.1167/iovs.12-9863
PURPOSE. IL-27 has emerged as an important regulator of proinflammatory T-cell responses in animal models. We investigated the pathophysiological role of IL-27 in Vogt-Koyanagi-Harada (VKH) disease.METHODS. IL-27P28 and EBI3 mRNA expression in peripheral blood mononuclear cells (PBMCs) were assayed by RT-PCR. Cytokines in the serum and supernatants of PBMCs, naive CD4(+) T cells and DC-T cocultures were assayed by ELISA. Flow cytometry was used to evaluate the frequencies of IL-17-producing CD4(+) T cells.RESULTS. The active VKH patients showed a decreased IL-27P28 mRNA expression in PBMCs and lower IL-27 expression in the serum and supernatants of PBMCs, but higher Th17 cells in PBMCs. EBI3 mRNA expression was not different among the groups tested. Stimulation of naive CD4(+) T cells under Th17 polarizing conditions showed a higher Th17 cell differentiation in active VKH patients. IL-27 significantly inhibited Th17 cell differentiation. IL-27-treated DCs showed a significant inhibition on Th17 differentiation. There was a significant defect in the Tr1 cell induction as measured by IL-10 in active VKH patients. Treatment with corticosteroids and cyclosporine A (CsA) resolved the intraocular inflammation in association with an upregulation of IL-27 and a downregulation of IL-17. In vitro experiments showed that corticosteroids, but not CsA, significantly upregulated the expression of IL-27.CONCLUSIONS. The present study suggests that decreased IL-27 expression may result in a higher Th17 in active VKH patients, which may promote the autoimmune response observed in these patients. Manipulation of IL-27 may offer a novel target for treatment of this disease. (Invest Ophthalmol Vis Sci. 2012; 53:4668-4675) DOI: 10.1167/iovs.12-9863