Wu Zhihui, Hu Mingzhi, Zhao Qiaoying, Lv Fengfeng, Zhang Jingying, Zhang Wei, Wang Yongfu, Sun Xiaolin, Wang Hui
Central Laboratory, First Affiliated Hospital of Baotou Medical College (Inner Mongolia Key Laboratory of Autoimmunology), Baotou 014010, Inner Mongolia Autonomous Region, China.
Department of Rheumatism and Immunology, First Affiliated Hospital of Baotou Medical College, Baotou 014010, Inner Mongolia Autonomous Region, China.
Beijing Da Xue Xue Bao Yi Xue Ban. 2024 Oct 18;56(5):860-867. doi: 10.19723/j.issn.1671-167X.2024.05.017.
To investigate the mechanism of immunomodulatory effects of umbilical cord mesenchymal stem cells (UC-MSCs) modified by miR-125b-5p on systemic lupus erythematosus (SLE).
The expression level of miR-125b-5p was detected by real-time fluorescence quantitative PCR in UC-MSCs and peripheral blood mononuclear cells (PBMCs) from SLE patients and health checkers. Annexin V-FITC/PI apoptosis detection kit was used to detect the effect of miR-125b-5p on apoptosis of UC-MSCs. MRL/lpr mice in each group were injected with UC-MSCs tail vein, and T-lymphocyte subsets in the spleen of the MRL/lpr mice were detected by flow cytometry after 5 weeks. The expression levels of interleukin (IL)-4 and IL-17A in serum of MRL/lpr mice were detected by ELISA. Hematoxylin-eosin staining was used to observe the pathological manifestations of the lungs and kidneys of the MRL/lpr mice.
miR-125b-5p was significantly down-regulated in PBMCs of SLE patients compared with healthy controls ( < 0.01). Compared with the UC-MSCs group, the expression of miR- 125b-5p in UC-MSCs modified by miR-125b-5p group was increased ( < 0.01). The survival rate of UC-MSCs was significantly increased by miR-125b-5p ( < 0.01). Compared with the untreated group of MRL/lpr mice, the expression level of IL-4 in serum was increased ( < 0.05); the expression level of IL-17A was decreased ( < 0.05); the proportion of Th17 cells in the spleen of MRL/lpr mice was decreased ( < 0.05); the inflammatory cells infiltration and micro-thrombosis of lungs and kidneys of MRL/lpr mice were significantly reduced in the UC-MSCs modified by miR-125b-5p treatment group.
UC-MSCs modified by miR-125b-5p have immunomodulatory effects on systemic lupus erythematosus.
探讨经miR-125b-5p修饰的脐带间充质干细胞（UC-MSCs）对系统性红斑狼疮（SLE）免疫调节作用的机制。
采用实时荧光定量PCR检测UC-MSCs以及SLE患者和健康体检者外周血单个核细胞（PBMCs）中miR-125b-5p的表达水平。使用膜联蛋白V-FITC/PI凋亡检测试剂盒检测miR-125b-5p对UC-MSCs凋亡的影响。每组MRL/lpr小鼠经尾静脉注射UC-MSCs，5周后通过流式细胞术检测MRL/lpr小鼠脾脏中的T淋巴细胞亚群。采用酶联免疫吸附测定法（ELISA）检测MRL/lpr小鼠血清中白细胞介素（IL）-4和IL-17A的表达水平。采用苏木精-伊红染色观察MRL/lpr小鼠肺和肾的病理表现。
与健康对照相比，SLE患者PBMCs中miR-125b-5p显著下调（<0.01）。与UC-MSCs组相比，经miR-125b-5p修饰的UC-MSCs组中miR-125b-5p的表达增加（<0.01）。miR-125b-5p显著提高了UC-MSCs的存活率（<0.01）。与未处理的MRL/lpr小鼠组相比，血清中IL-4的表达水平升高（<0.05）；IL-17A的表达水平降低（<0.05）；MRL/lpr小鼠脾脏中Th17细胞的比例降低（<0.05）；经miR-125b-5p处理的UC-MSCs组中，MRL/lpr小鼠肺和肾的炎性细胞浸润和微血栓形成明显减少。
经miR-125b-5p修饰的UC-MSCs对系统性红斑狼疮具有免疫调节作用。
