Systemic lupus erythematosus (SLE) is an autoimmune disease in which dysregulated T cell activity plays a central role in disease progression. Research explores how metabolic alterations in CD4+ T cells contribute to SLE pathogenesis and whether human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) can influence these metabolic processes to mitigate immune dysfunction.
A study published in Stem Cell Reviews and Reports analyzed clinical data and peripheral blood samples from 15 SLE patients and matched healthy controls. Researchers examined CD4+ T cell activity and metabolism using in vitro co-culture systems, Seahorse metabolic analysis, transcriptome sequencing, and Western blotting to assess metabolic enzyme expression.
The findings indicate that CD4+ T cells from SLE patients exhibit significantly elevated oxygen consumption rate (OCR) and glycolytic proton efflux rate (glycoPER), suggesting heightened metabolic activity compared to healthy controls. Following a 72-hour co-culture with hUC-MSCs, these metabolic markers, along with CD4+ T cell viability and pro-inflammatory cytokine levels, were significantly reduced. Additionally, gene expression analysis revealed upregulation of 434 genes and downregulation of 172 genes, with notable changes in the JAK-STAT and PI3K-Akt pathways—key regulators of immune activation and metabolism.
In lupus model mice, hUC-MSCs were found to suppress the expression of glucose metabolism-related enzymes and downregulate the JAK-STAT and PI3K-Akt pathways, further supporting their role in metabolic reprogramming of T cells. These results suggest that hUC-MSCs may exert therapeutic effects by modulating immune metabolism rather than broadly suppressing immune activity.
This study contributes to a growing body of evidence supporting the metabolic regulation of immune responses in autoimmune diseases. By targeting glycometabolism and signaling pathways, hUC-MSCs may offer a potential therapeutic avenue for SLE that differs from traditional immunosuppressive treatments.
