风湿

CD4⁺FOXP3⁺ T细胞与不明原因复发性流产

作者:Zhang XX 翻译:湖北省中医院熊丽桂 来源:中国风湿病公众论坛 日期:2017-10-12
导读

         CCL20/CCR6轴调控的CD4⁺FOXP3⁺ T细胞参与了不明原因复发性流产发病

        摘要:对不明原因的复发性流产患者CCR6/CCL20 在CD4(+)FOXP3(+)调节性T细胞中的功能和作用进行研究。采用流式细胞仪、逆转录-聚合酶链反应,酶联免疫吸附测定法、Western印迹和Transwell迁移实验来比较健康女性和复发性流产患者外周血及蜕膜中调节性T细胞的表达和功能。结果显示,复发性流产患者外周血及蜕膜组织中CD4(+)FOXP3(+) T 细胞和 CCR6(+)CD4(+)FOXP3(+) T细胞均较健康对照组低,FOXP3 和CCR6 mRNA表达水平也较健康对照组低(p<0.05),CCL20表达水平较正常对照组低(p<0.05)。在体外使用中和抗CCL20抗体时,调节性T细胞的迁移被明显抑制(达到89.13%)。而且发现,CCL20刺激剂可使调节性T细胞迁移增加3.2倍,而中和抗CCL20抗体可抑制调节性T细胞迁移。复发性流产患者上清液中CD4(+)CD25(+)CD127(dim/-) 调节性T细胞中的IL-10浓度明显低于对照组。当外周血中CD4(+)CD25(+) T 细胞和 CD4(+)CD25(-) T 细胞存在细胞-细胞接触时,抗CCL20抗体抑制剂IL-10和IL-4能够增加干扰素γ和IL-17的水平。当细胞-细胞接触被半透性细胞膜阻挡时,检测结果没有差异。当CCL20-CCR6迁移至母胎界面时,CCL20-CCR6能够激活CD4(+)FOXP3(+) 调节性T细胞的免疫活性。这些结果阐明了调节性T细胞发挥抑制作用的途径。

        附原文:

        AbstractExpression and function of CCR6/CCL20 in CD4(+)FOXP3(+) regulatory T cells(Tregs) was investigated in unexplained recurrent miscarriage (URM) patients.Flow cytometry, reverse transcription-polymerase chain reaction, enzyme-linkedimmunosorbent assay, western blots, and Transwell migration assays were used toanalyze the expression and function of regulatory T cells in peripheral blood(PB) and decidual samples of women with URM and of healthy controls.Proportions of CD4(+)FOXP3(+) T cells and CCR6(+)CD4(+)FOXP3(+) T cells werelower in URM patients than in healthy controls for both PB lymphocytes anddecidual samples (P < 0.05). Expression levels of FOXP3 and CCR6 mRNA werelower in URM patients than in control subjects for PB and decidual samples (P< 0.05). CCL20 protein levels were lower in URM patients than in controls (P< 0.05). An effect of Treg migration was significantly blocked (by 89.13%)using a neutralizing anti-CCL20 antibody in vitro. Furthermore, CCL20-stimulatedTregs exhibited a 3.21-fold increase in migration and this was blocked using aneutralizing anti-CCL20 antibody. IL-10 concentration in culture supernatantsof CD4(+)CD25(+)CD127(dim/-) Tregs of URM patients was significantly lower thanthat in controls. Anti-CCL20 antibody inhibited IL-10 and IL-4 expression butincreased IFN-r and IL-17 levels when there was cell-cell contact between PBCD4(+)CD25(+) T cells and CD4(+)CD25(-) T cells. No difference was detectedwhen cell-cell contact was prevented by a semi-permeable Transwell membrane.CCL20-CCR6 could drive immune activity of CD4(+)FOXP3(+) Tregs, followed bytheir migration to the feto-maternal microenvironment. These results elucidatedthe mechanism by which Tregs exert this suppressive effect.

        引自:Zhang XX et al.Regulation of CD4⁺FOXP3⁺ Tcells by CCL20/CCR6 axis in early unexplained recurrent miscarriagepatients.Genet Mol Res. 2015 Aug 7;14(3):9145-54.

分享:

评论

我要跟帖
发表
回复 小鸭梨
发表

copyright©医学论坛网 版权所有,未经许可不得复制、转载或镜像 京ICP证120392号 京公网安备11010502031486号

京卫网审[2013]第0193号

互联网药品信息服务资格证书:(京)-经营性-2012-0005

//站内统计 //百度统计 //站长统计
*我要反馈: 姓    名: 邮    箱: