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目的:探讨在脓毒症状态下白细胞介素(IL)-37对调节性T细胞(Treg)免疫功能影响。方法:分离纯化C57BL/6J小鼠脾脏Treg,进行体外培养,并将细胞分为健康对照组,脂多糖(LPS)组、IL-37组、LPS+IL-37组、LPS+3-Methyladenine (3-MA)组、LPS+3-MA+IL-37组、LPS+雷帕霉素(rapamycin)组、LPS+雷帕霉素+IL-37组。细胞培养24 h、48 h及72 h后,分别收集培养上清液及细胞,通过ELISA法检测Treg中IL-10和TGF-β分泌情况,采用流式细胞仪检测叉头翼状转录因子(Foxp3)和细胞毒性T淋巴细胞相关抗原4 (CTLA-4)的表达;并应用透射电子显微镜观察细胞自噬小体的形成及数目,Western blot检测自噬相关蛋白LC3I/Ⅱ以及Beclin1表达。此外,采用盲肠结扎穿孔术构建小鼠脓毒症模型,记录并比较各组小鼠生存率差异。结果:在LPS刺激Treg 24 h、48 h及72 h后分别给予IL-37处理,观察到LPS与IL-37协同刺激72 h后Treg功能明显增强;分别予以LPS和IL-37刺激Treg细胞后,透射电镜下观察自噬小体的形成明显增多。分别用自噬激动剂雷帕霉素和自噬抑制剂3-MA预处理改变细胞自噬活性,发现3-MA处理组和对照组相比,Treg功能显著下降,雷帕霉素处理组Treg功能则出现增强。3-MA处理组上清液中TGF-β分泌水平明显下降,雷帕霉素处理组TGF-β分泌量则明显增加,而各组上清液中IL-10分泌水平差异无统计学意义。IL-37干预能提高脓毒症小鼠生存率,其中以IL-37预处理组效果最明显。结论:IL-37能以自噬依赖途径增强Treg免疫功能,进而维持脓毒症时机体免疫反应平衡,改善脓毒症小鼠预后。“,”Objective:To investigate the effect of interleukin (IL)-37 on the immune function of regulatory T cells (Treg) in sepsis.Methods:TTregs were isolated and purified from the spleen of C57BL/6J mice and cultured in vitro. The cells were divided into the control group, lipopolysaccharide (LPS) group, IL-37 group, LPS+IL-37 group, LPS+3-Methyladenine (3-MA) group, LPS+3-MA+IL-37 group, LPS+Rapamaycin group, and LPS+Rapamaycin+IL-37 group. Culture supernatants and cells were collected, respectively, after cell culture for 24, 48, and 72 h. The secretion of IL-10 and TGF-β by Tregs was detected by ELISA, expressions of forkhead wing-link transcription factor (Foxp3) and cytotoxic T lymphocytes antigen 4 (CTLA-4) were measured by flow cytometry. Formation and number of autophagosomes were observed by transmission electron microscope. Western blot was used to determine expressions of autophagy associated proteins, including LC3I/II and Beclin1. Cecal ligation and puncture (CLP) was used to construct septic mice model, and the differences in survival rates between the groups were recorded and compared.Results:IL-37 was given to Tregs at 24, 48, and 72 h after LPS stimulation. The function of Treg was significantly enhanced after 72 h of synergistically stimulation by both LPS and IL-37. After stimulation with LPS and IL-37, the formation of autophagosomes in Tregs was obviously increased under observation of transmission electron microscopy. Pretreatment with autophagy agonist Rapamycin and autophagy inhibitor 3-MA was applied for altering the activity of cell autophagy. It was noticed that immune function of Treg was significantly decreased in the 3-MA group compared with the control group, while it was enhanced in the Rapamycin group. Secretion of TGF-β in the 3-MA group presented with significant reduction, which showed a marked increase in the Rapamycin group. However, no significant differences were found in IL-10 levels among various groups. Administration of IL-37 improved the survival rates of septic mice, which was much more efficient by treatment prior to the onset of sepsis.Conclusions:IL-37 appears to be capable of augmenting immune function of Tregs in an autophagy-dependent pathway, which might contribute to maintaining homeostasis of immune response in the setting of sepsis, and further improves the survival and prognosis of septic mice.