Platelet-derived microparticles induce CD8+ T cell senescence in end-stage renal disease via the transfer of microRNA-550a-5p

Infection is a leading cause of high mortality in patients with chronic kidney disease (CKD), in which T cell dysfunction is considered as a typical feature in CKD patients. Although platelets are active participants in immune response, their role in regulating T cell function in CKD patients remains unclear. In this study, we demonstrate that CD8 ⁺ T cell senescence may be a major contributor to the immunosuppressed state of end-stage renal disease (ESRD) patients, and that platelets derived from ESRD patients can induce premature CD8 ⁺ T cell senescence, potentially through mediating mitochondrial dysfunction. Further investigations reveal that platelet-derived microparticles (PMPs) from ESRD patients 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 is capable of preventing platelet-induced CD8 ⁺ T cell senescence in ESRD 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 the ESRD-associated immunosenescence.