【摘要】 背景:Faecalibacterium prausnitzii（Fp）可促进Treg细胞的分化,淋巴细胞功能相关抗原-1（LFA-1）亦参与Treg细胞的分化调节。目的:探讨Fp对LFA-1基因敲除(LFA-1^-/-)的结肠炎小鼠中Treg细胞和细胞因子的影响。方法:将同样遗传背景下野生型小鼠和LFA-1^-/-小鼠随机分为野生型对照组、野生型治疗组、LFA-1^-/-对照组、LFA-1^-/-治疗组。小鼠饮用DSS溶液诱导结肠炎模型,治疗组小鼠予Fp灌胃。观察各组小鼠一般状况和组织病理学评分,以流式细胞术检测脾脏和肠系膜淋巴结中Treg细胞比例,ELISA法检测外周血清IL-10、TGF-β1含量,实时PCR法检测结肠组织IL-10、TGF-β1 mRNA表达。结果:与相应对照组相比,野生型治疗组结肠组织学评分显著下降（P<0.05）;野生型治疗组和LFA-1^-/-治疗组脾脏和肠系膜淋巴结中Treg细胞比例显著升高（P<0.05）,血清IL-10、TGF-β1含量显著升高（P<0.01）,TGF-β1 mRNA表达显著升高（P<0.05）;LFA-1^-/-治疗组IL-10 mRNA表达显著降低（P<0.01）。与野生型治疗组相比,LFA-1^-/-治疗组血清TGF-β1含量显著降低（P<0.05）,IL-10、TGF-β1 mRNA表达显著降低（P<0.05）。结论:Fp在LFA-1^-/-小鼠中可上调Treg细胞比例,促进Treg细胞分泌抗炎因子IL-10、TGF-β1。Fp治疗野生型结肠炎小鼠的疗效优于LFA-1^-/-小鼠,可能与LFA-1缺失对Treg细胞功能的发挥和细胞因子分泌受限有关。更多还原

【Abstract】 Background:It has been widely accepted that Faecalibacterium prausnitzii（Fp）induces the differentiation of Treg cells.Lymphocyte function-associated antigen-1（LFA-1）is also involved in the differentiation of Treg cells.Aims:To investigate the effect of Fp on Treg cells and cytokines in colitis mice with LFA-1 knockout(LFA-1^-/-).Methods:Twenty wild type mice and twenty LFA-1^-/-mice with same genetic background were randomly divided into wild type control group,wild type treatment group,LFA-1^-/-control group and LFA-1^-/-treatment group.Colitis model was induced by drinking DSS solution.Mice in the two treatment groups were intragastrically administrated with Fp.General status and histopathological score were assessed.Percentages of Treg cells in spleen and mesenteric lymph nodes were measured by flow cytometry.Serum levels of IL-10 and TGF-β1 were measured by ELISA.mRNA expressions of IL-10 and TGF-β1 in colonic tissue were detected by real time PCR.Results:Compared with corresponding control groups,histopathological score was significantly decreased in wild type treatment group（P<0.05）;percentages of Treg cells in spleen and mesenteric lymph nodes were significantly increased（P<0.05）,serum levels of IL-10 and TGF-β1 were significantly increased（P<0.01）,expression of TGF-β1 mRNA was significantly increased in wild type treatment group and LFA-1^-/-treatment group（P<0.05）;expression of IL-10 mRNA was significantly decreased in LFA-1^-/-treatment group（P<0.01）.Compared with wild type treatment group,serum level of TGF-β1 was significantly decreased（P<0.05）,and mRNA expressions of IL-10 and TGF-β1 were significantly decreased in LFA-1^-/-treatment group（P<0.05）.Conclusions:Fp can up-regulate the percentages of Treg cells and enhance the secretion of anti-inflammatory cytokines IL-10 and TGF-β1 in LFA-1^-/-mice.The therapeutic efficacy for colitis in wild type mice is superior to that in LFA-1^-/-mice,which may be related to the inhibition of function of Treg cells and secretion of cytokines due to LFA-1 knockout.更多还原