中国血吸虫病防治杂志 ›› 2022, Vol. 34 ›› Issue (3): 277-.

• 论著 • 上一篇    下一篇

基于miRNA表达谱解析细粒棘球蚴病患者体内Th17/Treg失衡机制

鲁迪1,2△,宋佳卉3△,马子建2,4,张鹏越4,许磊1,韦川1,陈颖1,周莎1,朱继峰1,李娅琳1, 赵嘉庆5,朱明星5,赵瑞6,王海7,陈晓军1,赵巍5*,苏川1,2*   

  1. 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
  • 出版日期:2022-07-06 发布日期:2022-07-06
  • 作者简介:鲁迪,女,硕士研究生。研究方向:寄生虫感染与免疫 宋佳卉,女,硕士研究生。研究方向:棘球蚴病防治
  • 基金资助:
    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)

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

LU Di1, 2△, SONG Jia⁃hui3△, MA Zi⁃jian2, 4, ZHANG Peng⁃yue4, XU Lei1, WEI Chuan1, CHEN Ying1, ZHOU Sha1, ZHU Ji⁃feng1, LI Ya⁃lin1, ZHAO Jia⁃qing5, ZHU Ming⁃xing5, ZHAO Rui6, WANG Hai7, CHEN Xiao⁃Jun1, ZHAO Wei5*, SU Chuan1, 2*   

  1. 1 School of Basic Medical Sciences, Nanjing Medical University, Nanjing, Jiangsu 211166, China; 2 School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, China; 3 Medical Science and Technology Research Center, Ningxia Institute of Medical Science, Ningxia Medical University, Yinchuan, Ningxia 750004, China; 4 Nanjing Yike Population Health Research Institute, China; 5 Ningxia Key Laboratory of Prevention and Treatment of Common Infectious Diseases, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, Ningxia 750004, China; 6 Shizuishan Center for Disease Control and Prevention, Ningxia Hui Autonomous Region, China; 7 School of International Education, Nanjing Medical University, China
  • Online:2022-07-06 Published:2022-07-06

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。

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

Abstract: Objective To investigate the serum microRNA (miRNA) expression and examine the impact of miRNA expression 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 mTOR 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, and 15 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 infections, and differentially expressed miRNAs may lead to Th17/Treg imbalance through targeting the key transcription factors of Th17/Treg or PI3K⁃Akt and mTOR pathways, which facilitates the long⁃term parasitism of E. granulosus in hosts and causes a chronic disease. 

Key words: Echinococcus granulosus, microRNA, T helper type 17, regulatory T cell, Immune imbalance

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