Harnessing miR-16-5p-Loaded Exosomes from Adipose-Derived Stem Cells to Restore Immune Homeostasis in SLE Patients
Yinhong Zhang, Juan Chen, Wen-fei Mao, Li-xi Yan, Fei Long, Sheng-Hao Li, Ruixian Zhang
Abstract
BACKGROUND: Systemic Lupus Erythematosus (SLE) is an autoimmune disorder marked by an imbalance between pro-inflammatory Th17 cells and regulatory T cells (Tregs), which contributes to chronic inflammation and multi-organ damage, necessitating novel therapeutic strategies. METHODS: This study investigates the potential of adipose-derived stem cell (ADSC) exosomes to modulate the Th17/Treg balance in SLE patients through the miR-16-5p/LATS1 axis. Flow cytometry, ELISA, and quantitative real-time PCR were utilized to assess immune cell populations and cytokine levels in SLE patients. Additionally, ADSC exosomes were isolated and characterized, and their impact on CD4+ T cells was evaluated using dual-luciferase and Western blot assays. RESULTS: SLE patients exhibited increased Th17 cells and decreased Tregs, with corresponding changes in cytokine levels. Reduced miR-16-5p expression was noted in CD4+ T cells, correlating positively with Treg proportions. ADSC-derived exosomes were shown to deliver miR-16-5p effectively, targeting and downregulating LATS1 expression. This modulation restored the Th17/Treg balance and adjusted cytokine expression, indicating an immune regulatory effect. CONCLUSION: ADSC-derived exosomes, through the miR-16-5p/LATS1 axis, offer a promising therapeutic approach for SLE by restoring immune equilibrium. This study highlights the potential of exosome-based therapies in modulating immune responses, providing a foundation for developing innovative treatments for autoimmune diseases.