Department of Rheumatology and Immunology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
School of Pharmacy, Wenzhou Medical University, Wenzhou 325000, China.
Cells. 2022 Dec 19;11(24):4123. doi: 10.3390/cells11244123.
Umbilical cord blood mesenchymal stem cells (UC-BSCs) are cells with low immunogenicity and differentiation potential, and the transfer of exosomes carried by UC-BSCs can regulate innate and adaptive immunity and affect immune homeostasis. This is an area of focus for autoimmune illnesses such as systemic lupus erythematosus (SLE). The target of this research was to investigate the immunomodulatory effect of exosomes produced from mesenchymal stem cells on SLE and its mechanism. After isolation of peripheral blood mononuclear cells (PBMC) from the SLE group and healthy group and treatment of SLE-derived PBMCs with UC-BSC-derived exosomes, the mRNA levels of corresponding factors in cells under different treatments were determined by RT-PCR, Th17/Treg content was analyzed by FCM (flow cytometry), and the targeted binding of microRNA-19b (miR-19b) to KLF13 was identified by in vitro experiments and bioinformatics analysis. The findings demonstrated that PBMC cells from SLE patients had higher proportions of Th17 subsets than the control group, whereas Treg subgroups with lower percentages were discovered. miR-19b's expression level was markedly reduced, which was inversely associated to the concentration of KLF13. In vitro experiments show that UC-BSC-derived exosome treatment can target KLF13 expression by increasing the miR-19b level, thereby regulating Th17/Treg balance and inhibiting the expression of inflammatory factors. According to the study's findings, SLE patients have dysregulated expression of the genes miR-19b and KLF13, and UC-BSC exosomes could regulate Th17/Treg cell balance and inflammatory factor expression in SLE patients through miR-19b/KLF13.
脐带血间充质干细胞(UC-BSCs)是免疫原性低、分化潜能强的细胞,UC-BSCs 分泌的外泌体可以调节固有和适应性免疫,影响免疫稳态,这是系统性红斑狼疮(SLE)等自身免疫性疾病的研究重点。本研究旨在探讨间充质干细胞来源的外泌体对 SLE 的免疫调节作用及其机制。分离 SLE 组和健康组的外周血单个核细胞(PBMC),用 UC-BSC 衍生的外泌体处理 SLE 来源的 PBMC,通过 RT-PCR 测定不同处理下细胞中相应因子的 mRNA 水平,FCM(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 microRNA-19b(miR-19b)与 KLF13 的靶向结合。结果表明,SLE 患者 PBMC 细胞中 Th17 亚群比例高于对照组,而 Treg 亚群比例较低。miR-19b 的表达水平明显降低,与 KLF13 浓度呈负相关。体外实验表明,UC-BSC 衍生的外泌体处理可以通过增加 miR-19b 水平靶向调节 KLF13 表达,从而调节 Th17/Treg 平衡,抑制炎症因子的表达。根据研究结果,SLE 患者存在 miR-19b 和 KLF13 基因表达失调,UC-BSC 外泌体可能通过 miR-19b/KLF13 调节 SLE 患者 Th17/Treg 细胞平衡和炎症因子表达。