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

作　　者：杜露平[1,2] 鲁海燕 李明举 侯立婷 于晓明[1,2] 程海卫 张元鹏[1,2] 秦竹 李兰[1,2] 张浩明 杨利[1,2] 王义伟 陈瑾[1,2] 郑其升 侯继波[1,2] DU Luping;LU Haiyan;LI Mingju;HOU Liting;YU Xiaoming;CHENG Haiwei;ZHANG Yuanpeng;QIN Zhu;LI Lan;ZHANG Haoming;YANG Li;WANG Yiwei;CHEN Jin;ZHENG Qisheng;HOU Jibo(Institute of Veterinary Immunology&Engineering/National Research Center of Engineering and Technology for Veterinary Biologicals/Jiangsu Key Laboratory for Food Quality and Safety-State Key Laboratory Cultivation Base,Ministry of Science and Technology,Jiangsu Academy of Agricultural Sciences,Nanjing 210014,China;GuoTai(Taizhou)Center of Technology Innovation for Veterinary Biologicals,Taizhou 210014,China;Yantai Center for Animal Disease Control and Prevention,Yantai 264600,China)

机构地区：[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 [2]兽用生物制品(泰州)国泰技术创新中心,江苏泰州225300 [3]烟台市动物疾病预防与控制中心,山东烟台264033

出　　处：《中国农业大学学报》2025年第1期179-187,共9页Journal of China Agricultural University

基　　金："十四五"重点研发专项(2022YFD1800800);国家自然科学基金项目(32102690);江苏省农业自主创新专项(CX(21)3135)。

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RORγt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。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 RORγwere 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 

分 类 号：S852.4[农业科学—基础兽医学]