Pan F, Xiang H, Yan J, Hong L, Zhang L, Liu Y, Feng X, Cai C
The Affiliated Hospotal of Hangzhou Normal University, Hangzhou, China.
Scand J Immunol. 2017 Jun;85(6):441-449. doi: 10.1111/sji.12550.
Dendritic cells (DCs) are critical regulators of immune responses. This study was to observe the effect of DCs from peripheral blood on the differentiation of Th17 in patients with rheumatoid arthritis (RA). Peripheral blood samples were collected from 30 patients with RA and 20 healthy controls, respectively. Flow cytometry results showed that in contrast to Treg cells, the proportion of Th17 cells in T cells and the Th17/Treg ratio were both increased in patients with RA. The RT-PCR results showed that Foxp3、ROR γt and miR-363 expression in PBMC of patients with RA were reduced, but the ITGAV expression was increased, which was negatively related to miR-363 expression. IL-17, TGF-β and IL-6 levels detected by ELISA were increased in peripheral blood serum of patients with RA. Moreover, we noted that the CD11C αν /CD11C DCs ratio was obvious increased in patients with RA and has positive correlation to the Th17/Treg ratio. In cocultured system, Th17 cell differentiation was significantly inhibited in the presence of ITGF-β suggesting that Th17 cell differentiation was controlled by active TGF-β (aTGF-β). After DCs transfecting with miR-363 mimics and cocultured with T cells, Th17 cell number, IL-17 level and ROR-γt expression were significantly reduced in the presence of latent TGF-β (ITGF-β). In addition, the integrin αv protein expression was both reduced in the presence of aTGF-β or ITGF-β. These data demonstrated that DCs induced Th17 cell differentiation through miR-363/Integrin αv/TGF-β pathway in patients with RA.
树突状细胞（DCs）是免疫反应的关键调节因子。本研究旨在观察类风湿关节炎（RA）患者外周血DCs对Th17分化的影响。分别采集30例RA患者和20例健康对照者的外周血样本。流式细胞术结果显示，与调节性T细胞（Treg细胞）相比，RA患者T细胞中Th17细胞比例及Th17/Treg比值均升高。逆转录聚合酶链反应（RT-PCR）结果显示，RA患者外周血单个核细胞（PBMC）中叉头框蛋白3（Foxp3）、维甲酸相关孤儿受体γt（RORγt）和微小RNA-363（miR-363）表达降低，但整合素αV（ITGAV）表达升高，且与miR-363表达呈负相关。酶联免疫吸附测定（ELISA）检测显示，RA患者外周血血清中白细胞介素-17（IL-17）、转化生长因子-β（TGF-β）和白细胞介素-6水平升高。此外，我们注意到RA患者CD11C αν/CD11C DCs比值明显升高，且与Th17/Treg比值呈正相关。在共培养体系中，存在活性转化生长因子-β（aTGF-β）时，Th17细胞分化受到显著抑制，提示Th17细胞分化受aTGF-β调控。用miR-363模拟物转染DCs并与T细胞共培养后，在存在潜伏性转化生长因子-β（ITGF-β）的情况下，Th17细胞数量、IL-17水平及ROR-γt表达均显著降低。此外，在aTGF-β或ITGF-β存在的情况下，整合素αv蛋白表达均降低。这些数据表明，在RA患者中，DCs通过miR-363/整合素αv/TGF-β途径诱导Th17细胞分化。
