School of Medicine, Wuhan University of Science and Technology, Wuhan 430065, Hubei Province, China.
Basic Medical Laboratory, General Hospital of the Central Theater Command, Wuhan 430070, Hubei Province, China.
J Immunol Res. 2023 May 12;2023:3177584. doi: 10.1155/2023/3177584. eCollection 2023.
Excessive proliferation and activation of B cells, resulting in the production of various autoantibodies, is a crucial link and significant feature of the pathogenesis of systemic lupus erythematosus (SLE), as well as the pathological basis of systemic multiorgan damage. However, whether exosomes derived from human umbilical cord mesenchymal stem cells (hucMSCs-Exo) are involved in the immune regulation of SLE has not been clarified.
Therefore, our study aimed to investigate the efficacy of hucMSCs-Exo for treating SLE.
hucMSCs-Exo and peripheral blood mononuclear cells (PBMCs) of SLE patients were cocultured , and B cell apoptosis, activation, proliferation, and inflammation levels were detected by flow cytometry. Subsequently, the expression level of miR-155 in B lymphocytes of SLE patients was detected by qRT-PCR, and the target gene relationship between miR-155 and SHIP-1 was found through bioinformatics and dual luciferase activity experiments, which verified the inhibition of miR-155 in B lymphocytes of SLE patients to regulate immunity.
We found that hucMSCs-Exo promoted B cell apoptosis, prevented B cell overactivation, and reduced inflammation. MicroRNA-155 (miR-155) has a powerful regulatory function in B cells. It was demonstrated that hucMSCs-Exo acts synergistically with miR-155 inhibitors to target SHIP-1 to B cells more effectively than exosomes alone.
Our results provide insight into how hucMSCs-Exo regulates autoimmunity in patients with lupus and suggest targeting miR-155 for autoimmunity while protecting immunity.
B 细胞过度增殖和活化,导致产生各种自身抗体,是系统性红斑狼疮(SLE)发病机制的关键环节和重要特征,也是全身多器官损伤的病理基础。然而,人脐带间充质干细胞(hucMSCs)衍生的外泌体(hucMSCs-Exo)是否参与 SLE 的免疫调节尚不清楚。
因此,本研究旨在探讨 hucMSCs-Exo 治疗 SLE 的疗效。
将 hucMSCs-Exo 与人 SLE 患者的外周血单个核细胞(PBMC)共培养,通过流式细胞术检测 B 细胞凋亡、活化、增殖和炎症水平。随后,通过 qRT-PCR 检测 SLE 患者 B 淋巴细胞中 miR-155 的表达水平,通过生物信息学和双荧光素酶活性实验发现 miR-155 与 SHIP-1 的靶基因关系,验证 miR-155 在 SLE 患者 B 淋巴细胞中对免疫的抑制作用。
我们发现 hucMSCs-Exo 促进 B 细胞凋亡,防止 B 细胞过度激活,并降低炎症水平。微小 RNA-155(miR-155)在 B 细胞中具有强大的调节功能。研究表明,hucMSCs-Exo 与 miR-155 抑制剂协同作用,比单独使用外泌体更有效地靶向 B 细胞中的 SHIP-1。
我们的研究结果为 hucMSCs-Exo 如何调节狼疮患者的自身免疫提供了深入的见解,并提示针对 miR-155 治疗自身免疫,同时保护免疫。