DC-SIGN在结肠炎模型小鼠肠上皮细胞表达及其黏膜损伤的免疫调节  

Expression of DC-SIGN on intestinal epithelial cells and its immunity regulation in the model of mouse inflammatory bowel disease

作　　者：曾敬清[1] 刘伟[1] 林凯[1] 杨芬[1] 张彦洁[1] 章丽雅[1] 王俊祺[2] 周同[1,2] 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 [2]上海交通大学医学院附属瑞金医院儿科实验室,上海200025

出　　处：《现代免疫学》2012年第2期103-108,共6页Current Immunology

基　　金：国家自然科学基金资助项目(81000163;81170383;81070567);上海市科委基础研究重点项目(09JC1409900);上海市自然科学基金资助项目(10ZR1419600)

摘　　要：探讨固有免疫分子DC-SIGN在小鼠结肠炎肠上皮细胞表达及其干预效应,以及与炎症性肠病肠膜损伤的关系。建立葡聚糖硫酸钠诱导的小鼠结肠炎模型,随机分为正常对照组,模型组和单抗干预组,于建模后7d处死小鼠,取病变结肠组织并分离肠上皮细胞。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上皮细胞DC-SIGN表达;流式细胞术检测分离的肠上皮细胞DC-SIGN、CD80、CD86表达;以及采用流式细胞术和ELISA分别测定肠上皮细胞与初始CD4+T细胞共培养后T细胞Th1、Th2分化以及细胞因子分泌格局。结果显示,伴随小鼠结肠炎症及组织病理学改变,小鼠肠黏膜上皮细胞DC-SIGN表达增强,CD80、CD86相应上调,以及体外诱导T细胞向Th2为主分化且IL-4分泌增多。经针对凝集素功能域单抗干预后,可抑制肠上皮细胞DC-SIGN表达并相应下调CD80、CD86,以及抑制上皮细胞诱导T细胞向Th2分化的能力,且IL-4分泌减少及IL-4/IFN-γ比值降低,进而减轻了小鼠的结肠炎症损伤。结果表明,肠上皮细胞在小鼠结肠炎中可表达树突状细胞(DC)表型DC-SIGN,并具有诱导初始T细胞向Th2分化为主的DC样细胞功能,DC-SIGN可能介导肠上皮细胞在炎症性肠病及黏膜损伤机制中发挥了重要作用。To explore 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 pathology of intestinal mucosal lesion of inflammatory bowel disease （IBD）, a dextran sulfate sodium （DSS）-induced colitis model was established. Mice were randomly divided into three groups, namely control, DSS and PsL-EGFmAb-treated groups, which were all sacrificed after 7 days, fol- lowed by isolation of colon tissue and IECs. The tissue and pathological lesions were assessed by disease activity index （DAD and histopathological score. The expression of DC-SIGN in intestinal mucosal tissue was detected by immunohistochemistry. Flow cytometry was performed to detect the expression of DC-SIGN, CD80 and CD86 on IECs isolated from the mice. The capacity of mice IECs to activate T cells was determined by mixing them with naive CD4^＋ T ceils, the Thl/Th2 differentiation and the secretion of IL-4 and IFN-y were detected by flow cytomerty and ELISA respectively. The results showed that intesti hal inflammation is associated with changes in IECs including upregulation of the expression of DC-SIGN, CD80, CD86 and the improvement of their ability to induce T cells secreting IL-4. When interfering with PsL-EGFmAb, the expression of above molecules downregulated, and the secretion of IL-4 decreased as well as the ration of IL-4/IFN-γ, with the alleviation of colitis. In summary,our study demonstrated that IECs could express DC-SIGN, and are capable of inducing the differentiation of T cells into Th2 cells, which indicats that DC-SIGN might play an important role in the mechanism of intestinal mucosal lesions or inflammatory bowel disease.

关 键 词：炎症性肠病 肠上皮细胞 固有免疫分子 DC—SIGN 免疫调节 

分 类 号：R392.12[医药卫生—免疫学]