免疫增强剂CVC1302介导Tfh细胞分化机制分析
Analysis of the mechanism of immunopotentiator CVC1302 promoting the differentiation of follicular helper T cells
杜露平 1鲁海燕 1李明举 2侯立婷 1于晓明 1程海卫 1张元鹏 1秦竹 1李兰 1张浩明 1杨利 1王义伟 1陈瑾 1郑其升 1侯继波1
作者信息
- 1. 江苏省农业科学院动物免疫工程研究所/国家兽用生物制品技术创新中心/江苏省食品质量安全重点实验室,南京 210014;兽用生物制品(泰州)国泰技术创新中心,江苏泰州 225300
- 2. 烟台市动物疾病预防与控制中心,山东烟台 264033
- 折叠
摘要
为探究CVC1302调控滤泡辅助性T细胞(Tfh)分化的机制,本研究体外利用GM-CSF刺激培育小鼠骨髓树突状细胞(DC),CVC1302刺激后,分别检测IL-6、IL-21转录及表达水平;利用体外细胞共培养试验,检测Tfh、Th1、Th2和Th17分化关键转录因子Bcl-6、T-bet、GATA3和RORyt的转录水平,STAT3信号通路活化水平,Tfh细胞占CD4+T细胞比例及STAT3信号通路抑制后反向验证Tfh细胞占CD4+T细胞比例.结果表明:1)免疫增强剂CVC1302极显著促进小鼠骨髓DC分泌IL-6和IL-21.2)细胞共培养试验显示,CVC1302可显著促进STAT3磷酸化水平,表明STAT3信号通路被激活.3)利用STAT3信号通路抑制剂后,CD4+T细胞分化为Tfh细胞的水平显著降低,表明CVC1302依赖STAT3信号通路激活介导初始CD4+T细胞分化为Tfh细胞.综上,本研究推断CVC1302通过促进DC分泌IL-6和IL-12,并激活STAT3信号通路介导Tfh细胞的分化,旨在为后续免疫增强剂的开发提供思路.
Abstract
In order to explore the immune-mechanism of immunopotentiator CVC1302 mediate the differentiation of follicular helper T cells(Tfh),GM-CSF-cultured DC were stimulated with OVA plus CVC1302,then the transcription and expression levels of IL-6 and IL-21 were detected.In the cell co-culture test in vitro,the transcription levels of Bcl-6,Maf,T-bet,GATA3 and RORy were detected,which were key transcriptional factors for Tfh,Th1,Th2 and Th17,the activated levels of STAT3 signaling pathway,as well as the ratio of Tfh cells in CD4+T cell.Furthermore,we detected the ratio of Tfh cells in CD4+T cell when inhibited the STAT3 signaling pathway.The results showed that:1)The immunopotentiator CVC1302 significantly promoted the expression of IL-6 and IL-12 in DC.2)CVC1302 significantly enhanced the phosphorylation levels of STAT3,which showed that CVC1302 activated the STAT3 signaling pathway.3)The ratios of Tfh cells in CD4+T cell was decreased after the STAT3 signaling pathway inhibited,which showed that CVC1302 induced the differentiation of Tfh cells dependent on the activation of STAT3 signaling pathway.In this study,we concluded that CVC1302 induced the expression of IL-6 and IL-12 in DC,then activated STAT3 in order to mediate the differentiation of Tfh cells,which shed light on the development of new immunopotentiators.
关键词
CVC1302/DC/STAT3/Tfh细胞Key words
Immunopotentiator CVC1302/Tfh cells/STAT3/IL-6/IL-12引用本文复制引用
出版年
2025
国家科技期刊平台
NSTL
万方数据