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Background <p>T cells play a crucial role in the pathogenesis of systemic lupus erythematosus (SLE), with their functions regulated by various metabolic pathways. This study explores SLE pathogenesis and the therapeutic effects of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) via metabolic reprogramming.</p> Methods <p>Clinical data and peripheral blood samples were collected from 15 SLE patients and matched healthy controls. CD4<sup>+</sup> T cells were isolated and activated in vitro with anti-CD3/CD28. Following 72&#xa0;h of co-culture with hUC-MSCs, CD4<sup>+</sup> T cell viability was assessed using the CCK-8 assay. The oxygen consumption rate (OCR) and glycolytic proton efflux rate (glycoPER) were measured with a Seahorse analyzer. Cytokine levels were detected by multiplex assay, and transcriptome sequencing was performed. Western blotting analyzed glucose metabolism-related enzymes and signaling pathways in lupus model mice.</p> Results <p>Compared to healthy controls, activated CD4<sup>+</sup> T cells from SLE patients exhibited significantly increased OCR and glycoPER levels (<i>P</i> &lt; 0.05). Following 72&#xa0;h of co-culture with hUC-MSCs, OCR, glycoPER, cell viability, and pro-inflammatory factors in SLE-CD4<sup>+</sup> T cells decreased markedly (<i>P</i> &lt; 0.01). Upregulation of 434 genes and downregulation of 172 genes was observed, particularly in the JAK-STAT and PI3K-Akt pathways. hUC-MSCs inhibited the expression of glucose metabolism-related enzymes and the JAK-STAT and PI3K-Akt signaling pathways in lupus model mice.</p> Conclusion <p>hUC-MSCs inhibited the proliferation and function of aberrant CD4<sup>+</sup> T cells in SLE patients by modulating glycometabolism and the JAK-STAT and PI3K-Akt signaling pathways, providing new insights into the therapeutic mechanisms of MSCs based on metabolic reprogramming.</p> Graphical Abstract <p></p>

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Human Umbilical Cord Mesenchymal Stem Cells for the Treatment of Systemic Lupus Erythematosus via Glucose Metabolism of CD4+T Cells

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年2月20日

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  • Meng Ding,
  • Lu Jin,
  • Shaoxin Cui,
  • Lin Yang,
  • Jingjing He,
  • Xiaoping Wang,
  • Fei Chang,
  • Qun Wang,
  • Xue Liu,
  • Hongtao Jin,
  • Shuran Song,
  • Min Shi,
  • Jingjing Yu,
  • Jun Ma,
  • Aijing Liu

摘要

Background

T cells play a crucial role in the pathogenesis of systemic lupus erythematosus (SLE), with their functions regulated by various metabolic pathways. This study explores SLE pathogenesis and the therapeutic effects of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) via metabolic reprogramming.

Methods

Clinical data and peripheral blood samples were collected from 15 SLE patients and matched healthy controls. CD4+ T cells were isolated and activated in vitro with anti-CD3/CD28. Following 72 h of co-culture with hUC-MSCs, CD4+ T cell viability was assessed using the CCK-8 assay. The oxygen consumption rate (OCR) and glycolytic proton efflux rate (glycoPER) were measured with a Seahorse analyzer. Cytokine levels were detected by multiplex assay, and transcriptome sequencing was performed. Western blotting analyzed glucose metabolism-related enzymes and signaling pathways in lupus model mice.

Results

Compared to healthy controls, activated CD4+ T cells from SLE patients exhibited significantly increased OCR and glycoPER levels (P < 0.05). Following 72 h of co-culture with hUC-MSCs, OCR, glycoPER, cell viability, and pro-inflammatory factors in SLE-CD4+ T cells decreased markedly (P < 0.01). Upregulation of 434 genes and downregulation of 172 genes was observed, particularly in the JAK-STAT and PI3K-Akt pathways. hUC-MSCs inhibited the expression of glucose metabolism-related enzymes and the JAK-STAT and PI3K-Akt signaling pathways in lupus model mice.

Conclusion

hUC-MSCs inhibited the proliferation and function of aberrant CD4+ T cells in SLE patients by modulating glycometabolism and the JAK-STAT and PI3K-Akt signaling pathways, providing new insights into the therapeutic mechanisms of MSCs based on metabolic reprogramming.

Graphical Abstract