IL-21/IL-21R信号在TNBS诱导小鼠炎症性肠病病变形成中的作用研究

The Role of IL-21/IL-21R Signaling in Pathogenesis of TNBS-Induced Inflammatory Enteric Disease in Mice

探讨IL-21/IL21R信号在炎症性肠病病变形成中对肠固有层辅助T细胞应答的调控机制。利用IL-21R基因敲除小鼠(IL-21R KO),建立TNBS诱导的炎症性肠病动物模型。监测小鼠体重及生存率;HE染色观察小鼠肠组织形态结构及炎症反应情况;分离和提取肠固有层淋巴细胞(lamina propria lymphocyte,LPL),应用流式细胞仪检测Th1、Th2、Th17、Treg细胞比例和绝对数;ELISA法检测LPL培养上清中的细胞因子(IFN-γ、IL-4、IL-17A、IL-10)的分泌。结果显示:与WT小鼠相比,IL-21R KO小鼠体重下降更快,生存率明显降低;HE染色显示IL-21R KO小鼠肠管上皮损伤严重、隐窝大面积消失、大量炎性细胞浸润,并侵犯到黏膜肌层;IL-21R KO小鼠肠固有层Th1细胞应答显著增强,相反Th2、Th17和Treg应答明显抑制。因此,IL-21/IL-21R信号通过调节小鼠肠固有层Th细胞应答,在TNBS诱导的肠炎病变形成中发挥重要的保护性作用。

Regulation mechanism of IL-21/IL-21R signaling on T helper cell responses during affection forming in intestinal lamina propria by intestinal inflammation was investigated. In this study, IL-21R gene was used to knock off mice (IL-21RKO), and establish TNBS-induced animal model of inflammatory enteric disease. Determined and tested body weight and survival rate of mice;HE staining to observe mice intestinal tissue structure and the conditions of inflammatory responses;isolated and separated intestinal lamina propria lymphocyte (LPL), and counted the Th1, Th2, Th17, and Treg cell proportion and absolute number applied with flow cytometer;ELISA to determine and test the secretion of cell factors (IFN-γ, IL-4, IL-17A, IL-10) in LPL culture supernatant. The results showed that as compared with WT mice, the body weight of IL-21R KO lose weight more quickly, and the survival rate reduced;HE staining showed that epithelium of mice intestinal duct got serious damage, recessus disappeared at large area, many inflammatory cells infiltrated, and invaded in muscularis mucosae;the Th1 cell response of IL-21R KO lamina propriae significantly enhanced, yet responses of Th2, Th17, and Treg contrarily inhibited. Therefore, IL-21/IL-21R signaling plays important protective role in the formation of TNBS induced enteritis affection in mice through regulating the Th cell response in their lamina propriae.