Exosomal miR-484 Impairs CD8+ T Cell Homeostasis in Sepsis through the YPEL1/Cyclin E Axis
Sepsis induces profound CD8+ T cell dysfunction, contributing to immunosuppression and poor outcomes. Exosomes mediate intercellular communication during sepsis, but the role of exosomal microRNAs in regulating CD8+ T cell homeostasis remains unclear. We prospectively enrolled sepsis patients and healthy controls to investigate plasma exosomes and CD8+ T cell responses. Exosomes from sepsis patients (SE) promoted CD8+ effector differentiation and dysregulated cell cycle progression compared to those from healthy donors (HE). miRNA sequencing identified miR-484 as the most upregulated miRNA in SE. Functionally, SE-derived miR-484 suppressed YPEL1 expression in CD8+ T cells, leading to increased Cyclin E levels and aberrant cell cycle distribution. Inhibition of miR-484 restored YPEL1 and normalized Cyclin E expression, which was associated with a reversal of the sepsis exosome-induced bias toward CD8+ effector differentiation. Our findings reveal that exosomal miR-484 impairs CD8+ T cell homeostasis in sepsis by targeting the YPEL1/Cyclin E pathway, highlighting a potential mechanism for immune dysregulation and a target for intervention.