半乳糖凝集素1在脐带来源间充质干细胞调控类风湿关节炎患者T细胞功能中的作用

发布时间：2018-04-18 22:04

本文选题：关节炎 + 类风湿　；参考：《北京大学学报(医学版)》2016年06期

【摘要】：目的:明确半乳糖凝集素1(galectin-1)在脐带间充质干细胞(umbilical cord mesenchymal stem cells,UCMSCs)调控类风湿关节炎(rheumatoid arthritis,RA)患者T细胞功能中的作用。方法:应用慢病毒构建galectin-1低表达的UC-MSCs,即UC-MSCs(Gal-1-),采用直接接触培养方式分别将UC-MSCs、UC-MSCs(Gal-1-)与RA患者的CD4~+T细胞共培养。设立阴性对照组(CD4~+T)、阳性对照组[CD4~+T培养过程中加入植物血凝素(phytohaemagg lutinin,PHA)2 mg/L]、UC-MSCs-CD4~+T共培养组、UC-MSCs(对照shRNA)-CD4~+T共培养组及UC-MSCs(Gal-1-)-CD4~+T共培养组。MTS法检测CD4~+T细胞增殖,ELISA方法检测共培养上清液中肿瘤坏死因子α(tumor necrosis factorsα,TNF-α)水平,流式细胞术检测Th1/Th2/Th17细胞亚型。结果:UC-MSCs和UC-MSCs(对照shRNA)与CD4~+T细胞共培养组可显著抑制PHA诱导的CD4~+T细胞增殖及TNF-α表达,而UC-MSCs(Gal-1-)组对此无明显抑制作用。与阴性对照组(8.51%±2.04%)相比,UC-MSCs及UC-MSCs(对照shRNA)组可显著抑制Th1细胞分化(分别为4.83%±1.37%和5.13%±0.87%,P值分别为0.012和0.018),而UC-MSCs(Gal-1-)组对此无明显抑制作用(6.41%±0.96%,P=0.101)。与阴性对照组相比,UC-MSCs及UC-MSCs(对照shRNA)组可上调Th2并下调Th17比例,但差异并无统计学意义,UC-MSCs(Gal-1-)组的这一作用不明显。结论:UC-MSCs可抑制RA患者CD4~+T细胞的增殖、活化并可降低Th1细胞比例,但敲低galectin-1分子的表达后该作用减弱,提示galectin-1参与了UC-MSCs抑制RA患者CD4~+T细胞功能的过程。
[Abstract]:Aim: to investigate the role of galactose-1galectin-1 in the regulation of T cell function in patients with rheumatoid arthritis (RA) by umbilical cord mesenchymal cord mesenchymal stem cells (UCMSCs).Methods: Lentivirus was used to construct the low expression UC-MSCs (UC-MSCs), or UC-MSCs Gal-1-T cells. The UC-MSCsSU UC-MSCs Gal-1 was co-cultured with the CD4T cells of RA patients by direct contact culture.A negative control group was established, and the positive control group [phytohaemagglutinin lutinin PHA2 mg/L] UC-MSCs-CD4T co-culture group (control shRNA-CD4T co-culture group and UC-MSCsGal-1-CD4T co-culture group. MTS method was used to detect the proliferation of CD4T cells by Elisa.The level of tumor necrosis factor 伪 necrosis factors 伪 (TNF- 伪) in supernatant,The subtypes of Th1/Th2/Th17 cells were detected by flow cytometry.Results the PHA induced proliferation of CD4T cells and the expression of TNF- 伪 were significantly inhibited in the two groups, but not in the UC-MSCs and UC-MSCsGal-1-treated groups, but not in the UC-MSCs and UC-MSCs co-cultured with CD4T cells, but the expression of TNF- 伪 was not significantly inhibited in the UC-MSCs and UC-MSCs Gal-1-treated groups.Compared with the negative control group (8.51% 卤2.04%), UC-MSCs and UC-MSCs significantly inhibited the differentiation of Th1 cells (4.83% 卤1.37% and 5.13% 卤0.87%, P = 0.012 and 0.018%, respectively).Compared with negative control group, UC-MSCs and UC-MSCs could up-regulate Th2 and down-regulate the proportion of Th17, but the difference was not significant in UC-MSCs Gal-1-treated group.Conclusion: WUC-MSCs can inhibit the proliferation of CD4T cells, activate the CD4T cells and decrease the proportion of Th1 cells in RA patients, but the expression of galectin-1 molecules is weakened after knockdown, suggesting that galectin-1 plays an important role in the inhibition of CD4T cell function in RA patients by UC-MSCs.
【作者单位】：北京大学第三医院风湿免疫科;
【基金】：国家自然科学基金(81273293)资助~~
【分类号】：R593.22

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