肠道菌群失调增加小鼠肠上皮内T淋巴细胞活化和促炎细胞因子分泌  

Intestinal dysbacteriosis promotes intestinal intraepithelial T lymphocyte activation and proinflammatory cytokine secretion in mice

作　　者：罗霞[1] 罗爽[1] 郑彦懿 温如燕[1] 邓向亮[1] 周联[1] 

机构地区：[1]广州中医药大学中药学院,广东广州510006

出　　处：《细胞与分子免疫学杂志》2016年第8期1031-1035,共5页Chinese Journal of Cellular and Molecular Immunology

基　　金：广东省自然科学基金(2015A030313344);广东省教育厅科研项目(2013LYM0014)

摘　　要：目的探讨肠道菌群失调对小鼠小肠上皮间淋巴细胞(i IEL)功能的影响。方法口服给予广谱抗生素头孢曲松钠造成菌群失调小鼠模型,用乙二胺四乙酸(EDTA)和二硫苏糖醇(DTT)消化上皮细胞,流式细胞术鉴定i IEL表型和T细胞亚群的比例,ELISA检测肠腔冲洗液中白细胞介素2(IL-2)、IL-6、γ干扰素(IFN-γ)水平,采用选择性培养基以及PCR检测肠道细菌的类别。结果与正常组相比,给予头孢曲松钠后小鼠肠道内细菌明显减少,真菌和酵母菌增多;i IEL中T淋巴细胞亚群的比例发生变化,其中γδT细胞比例明显升高;CD3+T细胞、CD8+T细胞以及T细胞受体(TCR)γδ+T细胞活化增加,肠腔内IL-2、IL-6、IFN-γ水平显著升高。结论肠道菌群失调导致定植抗力下降,真菌增多,微生物屏障功能被破坏,引起i IEL中T细胞活化增加,促炎细胞因子分泌增加,可能是菌群紊乱引起炎症性肠病的原因之一。Objective To study the effect of intestinal dysbacteriosis on mouse intestinal intraepithelial T lymphocytes （ilELs）. Methods The intestinal dysbacteriosis was induced in mice by oral administration of ceftriaxone sodium. The ilELs were digested with ethylene diaminetetraacetic acid （EDTA） and DL-dithiothreitol （DTT）. The phenotype of ilELs and the proportions of subsets of T cells were detected by flow cytometry; the concentrations of cytokines （IL-2, IL-6, IFN-γ） in the intestine were examined by ELISA; the intestinal bacteria were analyzed with selective medium and PCR. Results Compared with the control group, intestinal commensal bacteria in mice were significantly reduced after the administration of ceftdaxone sodium, but fungi and yeasts increased. The proportions of T cell subgroups in ilELs changed, in which the proportion of TCR γδ＋T cells significantly increased, and the activated CD3＋ T, CD8＋T and TCR γδ＋T cells increased. The concentrations of IL-2, IL-6 and IFN-γ were significantly raised in the intestine. Conclusion The dysbacteriosis results in the decrease of commensal bacteria, the increase of the fungus, UELs and the promotion of proinflammatory cytokine secretion the damage of microbial barrier, the more activated T cells in n the gut. This is probably one of the reasons for inflammatory bowel disease caused by dysbacteriosis.

关 键 词：上皮间淋巴细胞 肠道菌群 生物屏障 

分 类 号：R378.2[医药卫生—病原生物学]