项目名称： 胸腺基质淋巴生成素在乳腺癌患者调节性T细胞分化和Th细胞极化中的作用

项目编号： No.30872986

项目类型： 面上项目

立项/批准年度： 2009

项目学科： 轻工业、手工业

项目作者： 任秀宝

作者单位： 天津医科大学

项目金额： 30万元

中文摘要： 肿瘤微环境中存在CD4+CD25+调节性T细胞升高以及Th细胞比例失衡现象，本项目主要探讨TSLP在其中的作用。证实乳腺癌及肺癌组织中TSLP表达高于正常组织，并且与局部Tregs细胞数量相关。培养肿瘤患者外周血单核细胞来源的树突状细胞，并设TSLP处理组（TSLP-DCs）、LPS处理组（LPS-DCs）和不经刺激的未成熟DC组（imDCs），TSLP-DCs高表达CD86, CD11C和HLA-DR，而CD83表达高于imDCs低于LPS-DCs，呈中度成熟DC表型。TSLP-DCs低分泌IL-6, IL-12, IL-10, TNF-αIFN-γ65292;而TGF-β20998;泌水平显著高于其他两组。将以上三组DC与CD4+CD25-T细胞共培养后，TSLP-DCs组中Tregs细胞的比例明显高于imDCs和LPS-DCs组；Transwell实验提示TSLP-DCs可以诱导Tregs细胞的趋化。同时，TSLP-DCs可以诱导CD4+T向Th2类细胞分化。以上结果提示TSLP可以通过诱导Tregs细胞上调和Th2类反应等方式，参与肿瘤局部的免疫抑制作用。

中文关键词： 胸腺基质淋巴生成素; 肿瘤; CD4+CD25+调节性T细胞；辅助性T细胞

英文摘要： The purpose of this project was to investigate the role of TSLP in the increasing prevalence of Tregs and differentiation of Th cells in cancer microenvironment. The results indicated that the expression ratio of TSLP in tumor tissues was significantly increased compared with that in normal tissue. The prevalence of Tregs in tumor microenvironment was correlated with the expression of TSLP. Dendritic cells (DCs) were induced from peripheral blood mononuclear cells collected from cancer patients and left unstimulated (imDCs) or exposed to hTSLP (TSLP-DCs) or LPS (LPS-DCs). TSLP-DCs expressed intermediate levels of CD83 and high levels of CD86, CD11C, and HLA-DR, which showed a characteristic of less mature DCs. TSLP-DCs secreted low levels of IL-6, IL-12, IL-10, TNF-αd IFN-γand high levels of TGF-βd MDC. The percentage of Tregs in CD4+CD25-T cells cocultured with TSLP-DCs group was statistically higher than that of LPS-DCs and imDCs. Transwell assays showed that TSLPDCs exhibited increased ability to attract the migration of CD4+CD25+Tregs, when compared with imDCs. TSLP-DCs induced CD4+T cells differentiate into Th2 cells. These results indicated that TSLP participated into the immune suppression in tumor microenvironment via inducing the increased prevalence of regulatory T cells and diffrentiation of CD4+T cells into Th2 cells.

英文关键词： Thymic stromal lymphopoietin; TSLP; cancer; regulatory T cell;Treg; helper T cell; Th