Platelet-derived microparticles induce CD8+ T cell senescence in chronic kidney disease via the transfer of microRNA-550a-5p.

Infection is a leading cause of mortality in patients with chronic kidney disease (CKD), in which T cell dysfunction is considered a typical feature. Although platelets are active participants in immune response, their role in regulating T cell function in patients with CKD remains unclear. In this study, we demonstrate that CD8+ T cell senescence may be a major contributor to the immunosuppressed state of patients with CKD, and that platelets derived from patients with CKD can induce premature CD8+ T cell senescence, potentially through mediating mitochondrial dysfunction. Further investigations reveal that platelet-derived microparticles (PMPs) from patients with CKD promote CD8+ T cell senescence via transferring miR-550a-5p, thereby decreasing PMPCB expression and inducing NDUFS8 cleavage failure. Finally, inhibition of miR-550a-5p and pretreatment with nicotinamide mononucleotide are capable of preventing platelet-induced CD8+ T cell senescence in CKD patients. Collectively, these findings suggest that the ectopic transient expression of platelet-derived miR-550a-5p in CD8+ T cells promotes cellular senescence by regulating the PMPCB-NDUFS8 axis, which can be exploited to treat CKD-associated immunosenescence.