UC-BSCs来源的外泌体对系统性红斑狼疮患者Th17/Treg平衡的影响  

The effect of UC-BSCs-derived exosomes on Th17/Treg balance in patients with systemic lupus erythematosus

作　　者：郑鑫[1,2] 吴玉玲 陈志涵[1,3] 陈琅[1,2] 魏旭华 陈义忠 ZHENG Xin;WU Yuling;CHEN Zhihan;CHEN Lang;WEI Xuhua;CHEN Yizhong(Fujian Medical University Provincial Clinical College,Fuzhou 350001,China;Department of Pediatrics,Fujian Provincial Hospital,Fuzhou 350001,China;Department of Rheumatology,Fujian Provincial Hospital,Fuzhou 350001,China;Department of Pediatrics,Shouning County Hospital,Ningde 355500,China;School of Basic Medicine Sciences,Fujian Medical University,Fuzhou 350122,China)

机构地区：[1]福建医科大学省立临床医学院,福州350001 [2]福建省立医院儿科,福州350001 [3]福建省立医院风湿科,福州350001 [4]寿宁县医院儿科,宁德355500 [5]福建医科大学基础医学院,福州350122

出　　处：《免疫学杂志》2023年第5期427-434,共8页Immunological Journal

基　　金：福建省自然科学基金面上项目(2021J01356)。

摘　　要：目的探究脐带血间充质干细胞(UC-MSC)来源的外泌体对系统性红斑狼疮(SLE)的免疫调节作用及其机制。方法分离SLE患者和健康对照人群外周血中的外周血单个核细胞(PBMC),使用UC-BSCs来源的外泌体处理SLE来源的PBMC,通过qRT-PCR分析不同处理后细胞中相应因子的mRNA水平,通过流式细胞术分析Th17/Treg含量,通过体外实验和生物信息学分析鉴定miR-19b与KLF13的靶向结合。结果相较于对照组人群,SLE患者来源的PBMC细胞中Th17亚群比例升高,同时Treg亚群比例降低,miR-19b水平明显降低且与KLF13水平负相关;体外实验显示,UC-BSC来源的外泌体处理可以调节Th17/Treg平衡,抑制炎症因子的表达。UC-BSC来源的外泌体能提高miR-19b水平进而靶向抑制KLF13表达。结论在SLE患者中,miR-19b与KLF13表达失调,而UC-BSC外泌体可以调节SLE患者Th17/Treg细胞平衡和炎症因子表达,这一过程可能与miR-19b/KLF13的相互作用有关。To investigate the immunomodulatory effect of umbilical cord blood mesenchymal stem cell(UCMSC)-derived exosomes on systemic lupus erythematosus(SLE)and its mechanism,peripheral blood mononuclear cells(PBMC)were isolated from SLE patients and healthy controls,and SLE-derived PBMC were treated with UCBSCs-derived exosomes.mRNA levels of the corresponding factors in the cells under different treatments were analyzed by RT-PCR,Th17/Treg levels were analyzed by flow cytometry,and the target binding of miR-19b to KLF13 was identified by in vitro experiments and bioinformatics analysis.Compared with the control population,the percentage of Th17 subpopulation was increased in PBMC cells from SLE patients,while the percentage of Treg subpopulation was decreased,the miR-19b levels were significantly down-regulated and negatively correlated with KLF13 levels;in vitro experiments showed that UC-BSC-derived exosomes could regulate the Th17/Treg balance and suppress the expression of inflammatory factors;UC-BSC-derived exosomes could increase miR-19b levels and thus target and inhibit KLF13 expression.In SLE patients,miR-19b and KLF13 expression are dysregulated.UC-BSC exosomes can regulate Th17/Treg cell homeostasis and inflammatory factor expression in SLE patients,which may be related to miR-19b/KLF13 interactions.

关 键 词：系统性红斑狼疮 脐带血间充质干细胞 免疫调节 外泌体 

分 类 号：R392.8[医药卫生—免疫学]