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Journal of Peking University (Health Sciences) ›› 2024, Vol. 56 ›› Issue (5): 860-867. doi: 10.19723/j.issn.1671-167X.2024.05.017

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Immunomodulatory mechanism of umbilical cord mesenchymal stem cells modified by miR-125b-5p in systemic lupus erythematosus

Zhihui WU1, Mingzhi HU1, Qiaoying ZHAO1, Fengfeng LV1, Jingying ZHANG2, Wei ZHANG1, Yongfu WANG2, Xiaolin SUN1,*(), Hui WANG2,*()   

  1. 1. Central Laboratory, First Affiliated Hospital of Baotou Medical College (Inner Mongolia Key Laboratory of Autoimmunology), Baotou 014010, Inner Mongolia Autonomous Region, China
    2. Department of Rheumatism and Immunology, First Affiliated Hospital of Baotou Medical College, Baotou 014010, Inner Mongolia Autonomous Region, China
  • Received:2021-07-26 Online:2024-10-18 Published:2024-10-16
  • Contact: Xiaolin SUN, Hui WANG E-mail:yolo_1010@126.com;wanghuier@126.com
  • Supported by:
    Supported by the National Natural Science Foundation of China(81860294);Supported by the National Natural Science Foundation of China(81860295);the Natural Science Foundation of Inner Mongolia(2019MS08055);the Inner Mongolia Autonomous Region Science and Technology Plan Projects(201802089);the Inner Mongolia Autonomous Region Science and Technology Plan Projects(2019GG052)

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Abstract:

Objective: 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). Methods: 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 via 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. Results: miR-125b-5p was significantly down-regulated in PBMCs of SLE patients compared with healthy controls (P < 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 (P < 0.01). The survival rate of UC-MSCs was significantly increased by miR-125b-5p (P < 0.01). Compared with the untreated group of MRL/lpr mice, the expression level of IL-4 in serum was increased (P < 0.05); the expression level of IL-17A was decreased (P < 0.05); the proportion of Th17 cells in the spleen of MRL/lpr mice was decreased (P < 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. Conclusion: UC-MSCs modified by miR-125b-5p have immunomodulatory effects on systemic lupus erythematosus.

Key words: Mesenchymal stem cells, Gene modification, Systemic lupus erythematosus, Immunomo-dulation, Umbilical cord

CLC Number: 

  • R593.2

Figure 1

miR-125b-5p expression in PBMCs from health control and SLE (n=19) HC, health control; SLE, systemic lupus erythematosus; PBMCs, peripheral blood mononuclear cells."

Figure 2

Expression of miR-125b-5p in transfected UC-MSCs (n=3) UC-MSCs, umbilical cord mesenchymal stem cells."

Figure 3

Apoptosis rate of UC-MSCs in each group *P < 0.05, * *P < 0.01, vs. UC-MSCs. UC-MSCs, umbilical cord mesenchymal stem cells; miR-NC, miR-negative control; A, Annexin V-FITC(-)/PI(-), living cell; B, Annexin V-FITC(+)/PI(-), viable apoptotic cell; C, Annexin V-FITC(+)/PI(+), non-viable apoptotic cell and dying cells."

Figure 4

Flow cytometry analysis of Th17, Treg, Th1, Th2 cells in MRL/lpr mouse spleen cells UC-MSCs, umbilical cord mesenchymal stem cells; miR-NC, miR-negative control; PBS, phosphate buffered saline; IL, interleukin; IFN-γ, inter-feron-γ."

Figure 5

Differentiation of T cell subsets in spleen cells of MRL/lpr mice in each group (n=4) UC-MSCs, umbilical cord mesenchymal stem cells; miR-NC, miR-negative control; PBS, phosphate buffered saline."

Table 1

Expression levels of IL-4 and IL-17A in serum of MRL/lpr mice in each group (n=4)"

Items Control PBS UC-MSCs UC-MSCs+miR-NC UC-MSCs+miR-125b-5p F P
IL-4/(ng/L) 242.53±5.38 247.13±8.40 250.55±5.67 249.22±4.14 251.94±6.02* 1.456 0.264
IL-17A/(ng/L) 131.65±20.04 113.85±26.17 143.03±14.90 139.14±5.38 101.23±12.90* 4.174 0.018

Figure 6

Pathological morphology of lung and kidney tissues in MRL/lpr mice in each group (HE ×22.9)"

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