Human umbilical cord mesenchymal stem cells for the treatment of systemic lupus erythematosus via glucose metabolism of CD4 + T cells

Abstract Background: T cells play a crucial role in the development of systemic lupus erythematosus(SLE), and their function is mediated by various metabolic pathways and enzyme activities. Here, we aim to analyze the phenotype of glucose metabolism of peripheral blood CD4+ T cells. Also, the effects of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) on the proliferation, function, and glucose metabolism of peripheral blood CD4+ T cells in SLE patients were assessed to elucidate the pathogenesis of SLE and the therapeutic mechanism of hUC-MSCs based on metabolic reprogramming. Methods: The clinical data and peripheral blood of 15 SLE patients and healthy controls were collected. CD4+ T cells were isolated via immunomagnetic beads followed by activation in presence of anti-CD3/CD28 in vitro. After 72h co-culture of with hUC-MSCs, CD4+ T cell viability was detected by CCK-8 assay. The Seahorse Bioscience XFe24 Extracellular Flux Analyzer was used to measure the oxygen consumption rate(OCR) and glycolytic proton efflux rate(glycoPER) of CD4+ T cells. Multiplex cytokine assay was conducted to detect the cytokines in the supernatant. The expression of genes was determined and identified by transcriptome sequencing. Results: Compared to the healthy controls, the OCR and glycoPER levels of activated CD4+ T cells were greatly increased in SLE (P<0.05). After 72h co-culture with hUC-MSCs, the OCR, glycoPER, cell viability and proinflammatory factors of SLE-CD4+ T cells decreased considerably(P<0.01). The mRNA levels of 434 genes were upregulated, and 172 genes were downregulated; this phenomenon was pronounced in the JAK-STAT and PI3K-Akt pathways. Conclusion: The levels of oxidative phosphorylation and glycolysis of CD4+ T cells were considerably increased in SLE patients, indicating that the glucose metabolism phenotype of CD4+ T cells, a potential therapeutic target, was closely related to the pathogenesis of the disease. hUC-MSCs reduced the proliferation activity of SLE-CD4+ T cells, altered the phenotype of glucose metabolism, reduced the level of proinflammatory factors, and increased the level of anti-inflammatory factors. The regulatory effects of MSC on the cellular energy metabolism phenotype may be related to the influence of JAK-STAT and PI3K-Akt signaling pathways.