肠上皮细胞DC-SIGN表达与幽门螺杆菌感染后结肠炎小鼠发病相关性研究  

Expression of DC-SIGN on intestinal epithelial cells and its immunity regulation in Helicobacter pylori infection of mouse inflammatory bowel disease

作　　者：杨芬[1] 曾敬清[1] 苏林[1] 王歆琼[1] 章丽雅[1] 吴菁[1] 任建敏[1] 刘伟[1] 周同[1] 许春娣[1] 

机构地区：[1]上海交通大学医学院附属瑞金医院儿科,上海200025

出　　处：《现代免疫学》2013年第1期23-29,共7页Current Immunology

基　　金：国家自然科学基金项目(81000163;81170383;81070567;81270801);上海市科委基础研究重点项目(No.09JC1409900);上海市自然科学基金项目(10ZR1419600)

摘　　要：探讨肠上皮细胞固有免疫分子DC-SIGN表达,以及对幽门螺杆菌(Helicobacter pylori,Hp)感染后结肠炎小鼠发病的调节作用。建立Hp感染后葡聚糖硫酸钠(DSS)诱导的结肠炎小鼠模型,随机分为正常组、DSS组、Hp+DSS组,于建模后7d处死小鼠,取小鼠病变结肠组织及脾脏,分别分离肠黏膜上皮细胞和脾脏细胞。采用疾病活动指数(DAI)评分和HE染色,进行组织损伤和病理学观察;免疫组化检测小鼠肠黏膜组织DC-SIGN表达;流式细胞术分别检测离体小鼠肠上皮细胞以及脾脏中树突状细胞(DC)的DC-SIGN、MHCⅡ、CD86表达;此外流式细胞术检测脾脏CD4^+T细胞的IFN-γ、IL-4分泌状况。结果显示,相较DSS结肠炎组肠黏膜组织DC-SIGN高表达,Hp感染的结肠炎小鼠肠黏膜组织DC-SIGN出现低表达,且小鼠结肠炎症及组织病理学改变均减轻于DSS结肠炎组。此外,小鼠离体肠黏膜上皮细胞以及脾脏中CD11c^+DC的DC-SIGN表达也均低于DSS结肠炎组,并伴随MHCⅡ、CD86相应下调。进一步发现,Hp感染的结肠炎小鼠脾脏CD4^+T细胞IL-4分泌及全身炎症程度均低于DSS结肠炎组。结果提示,Hp感染可下调肠黏膜上皮细胞DC-SIGN表达,减轻由后者介导上皮细胞的肠黏膜促炎作用和损伤,这一状况可能与Hp感染引发肠道黏膜以及全身炎症免疫状态下调或改变有关。This study aims to investigate the expression of dendritic cell-specific intercellular adhesion molecule-3-grabbing non- integrin（DC-SIGN）on intestinal epithelial cells （IECs） and its possible immunomodulatory effects on the intestinal mucosal le- sion of inflammatory bowel disease （IBD） in mice that have been infected with Helicobacter pylori（Hp）. The study consisted three groups of mice, the normal control group, the dextran sulfate sodium （DSS） induced colitis （DDS） group, and colitis group induced in the Hp infected mice （DSS with Hp infection group）. All the animals were sacrificed after 7 days, followed by isolation of colon tissue, intestinal epithelium cells （IECs） and the spleen was removed. The tissue lesion and pathological dam- age were assessed by disease activity index （DAD and histopathological score. The expression of DC-SIGN in intestinal mucosal tissues was detected by immunohistochemistry. Flow cytometry was performed to detect the expression of DC-SIGN, MHC II and CD86 on the IECs. In addition, the secretion of IL4 and IFN-y by the spleen cells were detected by flow cytomerty. The results showed that in DSS group DC-SIGN, MHC II and CD86 were upregulated on the IECs, with increasing of colon inflam- matory and histopathological lesions. Furthermore in DSS with Hp group, the expression of the above mentioned molecules were down-regulated, and the secretion of IL-4 and the number of CD4＋ T cell in the spleen were reduced. In summary, our study demonstrated that IECs could express DC-SIGN, and Hp infection could down-regulate its expression, which in turn could reduce the pro-inflammatory effects and damage mediated by the epithelial cells of the intestinal mucosa. This situation may be related to changes in systemic and intestinal mucosal immune reaction condition caused by Hp infection.

关 键 词：炎症性肠病 幽门螺杆菌 肠上皮细胞 DC—SIGN 免疫调节 

分 类 号：R574.62[医药卫生—消化系统]