基于miRNA表达谱解析细粒棘球蚴病患者体内Th17/Treg失衡机制  

Study on mechanisms of Th17/Treg imbalance in patients with cystic echinococcosis based on miRNA expression profiles

作　　者：鲁迪 宋佳卉 马子建 张鹏越 许磊 韦川 陈颖 周莎 朱继峰 李娅琳 赵嘉庆[5] 朱明星[5] 赵瑞[6] 王海 陈晓军 赵巍[5] 苏川[1,2] LU Di;SONG Jia-hui;MA Zi-jian;ZHANG Peng-yue;XU Lei;WEI Chuan;CHEN Ying;ZHOU Sha;ZHU Ji-feng;LIYa-lin;ZHAO Jia-qing;ZHU Ming-xing;ZHAO Rui;WANG Hai;CHEN Xiao-Jun;ZHAO Wei;SU Chuan(School of Basic Medical Sciences,Nanjing Medical University,Nanjing,Jiangsu 211166,China;School of Public Health,Nanjing Medical University,Nanjing,Jiangsu 211166,China;Medical Science and Technology Research Center,Ningxia Institute of Medical Science,Ningxia Medical University,Yinchuan,Ningxia 750004,China;Nanjing Yike Population Health Research Institute,China;Ningxia Key Laboratory of Prevention and Treatment of Common Infectious Diseases,School of Basic Medical Sciences,Ningxia Medical University,Yinchuan,Ningxia 750004,China;Shizuishan Center for Disease Control and Prevention,Ningxia Hui Autonomous Region,China;School of International Education,Nanjing Medical University,China)

机构地区：[1]南京医科大学基础医学院,江苏南京211166 [2]南京医科大学公共卫生学院,江苏南京211166 [3]宁夏医科大学医学科学技术研究中心、宁夏医学科学研究所,宁夏银川750004 [4]江苏省南京亿科人群健康研究院 [5]宁夏常见传染病防治研究重点实验室、宁夏医科大学基础医学院,宁夏银川750004 [6]宁夏回族自治区石嘴山市疾病预防控制中心 [7]南京医科大学国际教育学院

出　　处：《中国血吸虫病防治杂志》2022年第3期277-285,共9页Chinese Journal of Schistosomiasis Control

基　　金：西藏自治区科技计划项目(XZ201703⁃GB⁃01);宁夏回族自治区重点研发项目(2018BEG02003);宁夏回族自治区自然科学基金(2018AAC03209)。

摘　　要：目的观察细粒棘球蚴病患者血清微小RNA(miRNA)表达水平、探讨miRNA对辅助性T细胞17(Th17)/调节性T细胞(Treg)失衡的影响,以阐明细粒棘球蚴慢性感染并长期致病的机制。方法提取细粒棘球蚴病患者与健康对照者血清总RNA,采用Illumina测序平台进行高通量测序。分别采用miRBase数据库和miRDeep2工具进行已知miRNA注释和新miRNA预测,并进行差异分析。采用miRanda软件和TargetScan软件分别预测差异表达miRNA靶基因后取交集,进行基因本体(GO)富集分析以及京都基因和基因组百科全书(KEGG)通路分析。在差异表达变化倍数居前20位的miRNA中,匹配可靶向决定Th17细胞和Treg细胞生成的关键转录因子(RORC和FOXP3)或重要调控通路(PI3K⁃Akt和mTOR通路)相关基因的miRNA。结果细粒棘球蚴病患者与健康对照血清中共有53个差异表达miRNA,其中47个上调表达miRNA、6个下调表达miRNA。GO富集分析显示,差异表达miRNA功能涉及DNA转录翻译、细胞成分、细胞形态、神经发育及代谢分解等过程。KEGG富集分析显示,这些差异表达miRNA靶基因涉及的主要信号通路包括MAPK、PI3K⁃Akt、mTOR等信号通路。在差异表达变化倍数居前20位的miRNA中,有3个潜在靶向调控RORC的miRNA、15个潜在靶向PI3K⁃Akt、mTOR信号通路的miRNA。结论细粒棘球蚴感染后可使患者血清miRNA表达谱出现明显改变,差异表达miRNA可能通过靶向Th17/Treg关键转录因子或PI3K⁃Akt、mTOR通路而导致Th17/Treg免疫失衡,进而利于细粒棘球蚴在宿主体内长期寄生并慢性致病。Objective sion profiles on T helper type 17(Th17)/regulatory T cells(Treg) imbalance among patients with cystic echinococcosis, so as to provide insights into the illustration of the mechanisms underlying chronic Echinococcus granulosus infections, and long-term pathogenesis.Methods Total RNA was extracted from the sera of cystic echinococcosis patients and healthy controls, and subjected to high-throughput sequencing with the Illumina sequencing platform. Known miRNAs were annotated and new miRNAs were predicted using the miRBase database and the miRDeep2 tool, and differentially expressed miRNAs were identified. The target genes of differentially expressed miRNAs were predicted using the software miRanda and TargetScan, and the intersection was selected for Gene Ontology(GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis. Among the differentially expressed miRNAs with the 20 highest fold changes, miRNAs that targeted genes relating to key transcription factors RORC and FOXP3 that determine the production of Th17 and Treg cells or their important regulatory pathways(PI3K-Akt and mTOR pathways) were matched.Results A total of 53 differentially expressed miRNAs were screened in sera of cystic echinococcosis patients and healthy controls, including 47 up-regulated miRNAs and 6 down-regulated miRNAs.GO enrichment analysis showed that these differentially expressed miRNA were involved DNA transcription and translation, cell components, cell morphology, neurodevelopment and metabolic decomposition, and KEGG pathway analysis showed that the differentially expressed miRNA were mainly involved in MAPK, PI3K-Akt and m TOR signaling pathways. Among the differentially expressed miRNAs with the 20 highest fold changes, there were 3 miRNAs that had a potential for target regulation of RORC, and15 miRNAs that had a potential to target the PI3K-Akt and mTOR signaling pathways.Conclusions Significant changes are found in serum miRNA expression profiles among patients with E. granulosus inf

关 键 词：细粒棘球蚴 微小RNA 辅助性T细胞17 调节性T细胞 免疫失衡 

分 类 号：R532.32[医药卫生—内科学]