MiR-155在断奶期接力miR-146a介导肠上皮固有免疫耐受  

MiR-155 contributes to intestinal innate tolerance via replacing miR-146a in suckling-weaning transition

作　　者：张记[1] 田志强[1] 申子刚[1] 何海洋[1] 吴玉章[1] 李晋涛[1] 

机构地区：[1]第三军医大学全军免疫学研究所,重庆400038

出　　处：《免疫学杂志》2015年第6期471-475,共5页Immunological Journal

基　　金：重庆市科技攻关计划项目(CSTC2009AB5197);国家自然科学基金(81271813;81202326)

摘　　要：目的哺乳动物新生期肠上皮高表达mi R-146a介导固有免疫耐受,本研究探讨mi R-146a下降后肠上皮继续保持耐受状态的分子机制。方法定量PCR分析肠上皮mi R-146a与mi R-155表达模式,体外实验比较二者激活的刺激强度差异;转染及免疫印迹实验分析mi R-155在肠上皮免疫耐受中的功能及其可能调控靶标;小鼠提前断奶实验分析影响mi R-155激活的关键因素。结果肠上皮mi R-146a在新生期高表达并在断奶期降至极低水平,mi R-155则在断奶期剧烈上调;肠上皮中mi R-155激活强度显著高于mi R-146a;肠上皮高表达的mi R-155通过靶向抑制TAB2、IKKε、NIK等抑制炎症应答而非促进炎症;肠上皮mi R-155激活表达与哺乳动物断奶时间相关。结论哺乳动物肠道发育中,mi R-146a与mi R-155在断奶期发生功能接力,依次在新生期和成年期介导肠上皮固有免疫耐受。It has demonstrated that mi R-146 a mediates innate immune tolerance in neonate intestine,however, the mechanism that keeping intestinal epithelial innate immune tolerance after mi R-146 a declined is unknown. We used real time PCR to examine the expression pattern of mi R-146 a and mi R-155 in intestinal epithelial cells（IEC） at different days after birth. In vitro assay were used to examine their induction pattern and functions in limiting inflammatory response, while early-wearing assay was used to confirm their function in vivo.Our results showed that mi R-155 expression was low in neonatal period and dramatic increased at suckling-weaning transition. In vitro assay showed that the activated expression of mi R-155 in IEC was much higher than that of mi R-146 a and can exert negative regulation on pro-inflammatory signaling pathways through targeting TAB2, IKKε and NIK. In vivo assay indicted that the induction of mi R-155 in IEC was affected by wearing time and acted role mainly after weaning. Thus, our results identify that differential activated mi R-146 a and mi R-155 contribute to developmental intestinal innate tolerance in a transferred manner in suckling-weaning transition.

关 键 词：肠上皮细胞 MIR-155 免疫耐受 断奶过渡 

分 类 号：R392.9[医药卫生—免疫学]