异位灶微环境子宫内膜间质细胞对调节性T细胞的功能影响  

The functional regulation of endometrial stromal cells on Treg cells in the endometriotic milieu

作　　者：周文洁[1] 李大金[1] 王晓秋[1] 

机构地区：[1]复旦大学附属妇产科医院暨妇产科研究所,上海200011

出　　处：《现代免疫学》2014年第4期272-277,共6页Current Immunology

基　　金：国家自然科学青年科学基金(81200425);教育部高等学校博士学科点专项科研基金资助项目-新教师类(20110071120093)

摘　　要：本研究探讨了子宫内膜异位症异位病灶中调节性T细胞(Treg细胞)的功能调节及其分子机制。采用原代分离培养子宫内膜间质细胞(ESC),密度梯度离心法及磁珠分选法分离获得健康人外周血Treg细胞,分别建立ESC,Treg细胞单独培养,及ESC-Treg细胞共培养体系;并观察外源性促炎细胞因子白介素1-β(IL-1β)或肿瘤坏死因子-α(TNF-α)对调节性T细胞功能的影响。酶联免疫吸附试验(ELISA)法检测培养上清中转化生长因子-β1(TGF-β1)分泌水平;流式细胞术分析Treg细胞表面分子CTLA-4的表达以及胞内转录因子Stat3、Stat6和Foxp3的表达。结果显示:(1)ESC能够促进Treg细胞转录因子Foxp3及表面分子CTLA-4的表达。(2)ESC能够明显促进Treg细胞分泌TGF-β1;但IL-1β与TNF-α对TGF-β1的分泌没有明显的促进作用。(3)ESC明显上调Treg细胞转录因子Stat3和Stat6的表达;IL-1β和TNF-α均能够进一步增强对Stat3的表达;IL-1β还能进一步增强Stat6的表达。我们的研究提示,子宫内膜异位症异位病灶微环境中的ESC能够增强Treg细胞的免疫抑制能力,从而有利于异位内膜的种植生长。The study investigate the functional regulation of endometrial stromal cells on Treg cells in the ectopic milieu. The endometrial stromal cells （ESC） were separated from the eutopic endometrium of patients with endometriosis, and Treg cells were sorted by density gradient centrifugation and MACS. The ESC, regulatory T cells （Treg cells） culture alone or co-culture was established, respectively, and the coculture were then treated with recombinant human proinflammatory cytokines, IL-1β or TNF-α The TGF-β1 concentrations in culture supernatant were quantified by ELISA kits. The expression of CTLA-4 and transcription factor Stat3, Stat6 and Foxp3 were analyzed by FCM. The expression of CTLA-4 and Foxp3 were upregulated in Treg cells when cocultured with ESC. The secretion of TGF-β1 was increased significantly in Treg cells in coculture with ESC, IL-Iβ or TNF-α had no further role. The expression of Stat3 and Stat6 were upregulated in Treg cells when co-cultured with ESC, and both IL-1β and TNF-α had further promoted Stat3 expression, but only IL-1β had further promoted Stat6 expression in Treg. Our study suggested that the ESC from the eutopic endometrium could enhance the immune suppression of Treg cells, which is easy to form an immune tolerance milieu in the ectopic milieu in the pathogenesis of endometriosis.

关 键 词：子宫内膜异位症 子宫内膜间质细胞 调节性T细胞 功能调节 

分 类 号：R339.22[医药卫生—人体生理学]