白细胞介素-6在溃疡性结肠炎模型小鼠Th17/Treg细胞失衡中的作用

Role of IL-6 in the imbalance of Th17/Treg in DSS-induced ulcerative colitis mice

目的研究白细胞介素-6(IL-6)在溃疡性结肠炎(ulcerative colitis,UC)模型小鼠结肠固有层黏膜局部Th17和调节性T细胞(Treg)失衡中的作用。方法制备葡聚糖硫酸钠(DSS)诱导的UC模型小鼠(UC组,n=5),检测UC组小鼠和正常对照组小鼠(NC组,n=5)结肠固有层黏膜单个核细胞中Th17细胞及Treg细胞的水平,用CBA检测细胞培养上清IL-6、IL-10、IL-17等细胞因子的水平。结果在DSS诱导的UC小鼠结肠固有层黏膜中,Th17细胞水平均高于NC组(P<0.05);IL-17A水平高于NC组(P<0.05);Treg细胞水平显著高于NC组(P<0.05)。UC模型小鼠结肠固有层黏膜单核细胞培养上清液中IL-10表达水平均低于NC组(P<0.05)。UC模型小鼠血清及结肠固有层黏膜单核细胞中,IL-6的水平高于NC组(P<0.05),而在其他组织中,两组差异无统计学意义(P>0.05);在UC模型小鼠中,血清及结肠固有层单核细胞中IL-6的水平高于其他组织(P<0.05)。结论在UC模型小鼠结肠固有层黏膜中存在Th17/Treg细胞的失衡,局部IL-6升高参与了Th17/Treg细胞间的分化失衡,从而在UC模型小鼠的免疫异常发病中起重要作用。

Objective To investigate the role of IL-6 in the imbalance of T helper 17（Th17） cells and regulatory T（Treg） cells in colonic lamina propria mucous in dextran sulphate sodium（DSS） induced UC mice. Methods Male C57 BL/6 mice were divided into two groups,which named DSS induced ulcerative colitis（UC） group（n = 5）,and normal control（NC） group（n = 5）. The levels of the Th17 cells and Treg cells in colonic lamina propria mucous mononuclear cells were detected,and levels of cytokines IL-6,IL-10,IL-17 in cultured mononuclear cells in peripheral blood,mesenteric lymph node,lamina propria of jejunum and colon,spleen were measured by flowcytomix. Results In DSS induced UC models,Th17 cells in the lamina propria mucous membrane levels were higher than those in NC group（P〈0. 05）; IL-17 A levels were higher than those in NC group（P〈0. 05）. Treg cells levels were significantly higher than those in NC group（P〈0. 05）; IL-10 levels of UC group in the lamina propria mononuclear cell culture supernatant were lower than those in NC group（P〈0. 05）. In UC group,IL-6 levels in serum and in colonic lamina propria mononuclear cells,both were higher than those in NC group（P〈0. 05）,while in the other tissues there was no difference between two groups（P〈0. 05）. Conclusion There is an imbalance of Th17/Treg cells in UC,local increased IL-6 participated in the Th17/Treg cells differentiation between imbalances,and IL-6 plays an important role in the immunological pathogenesis of UC mice.