Suppression of NK cell function by platelet-derived microparticles: implications for transfusion-related immunomodulation

The immunomodulatory effects of platelet-derived microparticles (PMPs) on host innate immunity remain incompletely understood. In this study, we established a clinically relevant in vitro model using PMPs from stored platelets to investigate their effects on NK cell function. PMPs were isolated from platelets of 3 healthy donors, and co-cultured with PBMCs or primary NK cells from 18 healthy donors. Their effects on NK cell activation, cytotoxic function, and IFN-γ secretion were assessed by flow cytometry. qRT-PCR was performed to detect the mRNA expression of four key NK functional genes ( IFNG , GZMB , PRF1 and FOXO1) . High-throughput small RNA sequencing coupled with bioinformatic analysis was applied to screen PMP-derived miRNAs, and miR-223-3p was identified as a candidate functional mediator. We further conducted ex vivo validation of this effect using PBMCs from 12 sepsis patients. PMPs accumulating to estimated transfusion-relevant concentrations in stored platelets modulate NK cell activation, IFN-γ production, cytotoxic molecule expression and K562 cell killing in a concentration-dependent manner. Transcriptional detection results suggest that the downregulation of cytotoxic effector proteins induced by PMPs may be predominantly regulated by post-transcriptional pathways, which are possibly mediated by miR-223-3p. Our findings identify a potential pathway by which PMPs accumulating during platelet storage may contribute to transfusion-related immunomodulation, offering a preliminary mechanistic framework. Notably, the results of our ex vivo validation using samples from sepsis patients provide a foundation for the hypothesis that PMP-mediated NK cell modulation may contribute to immune dysregulation in clinical scenarios, such as sepsis, where platelet transfusions are common.