Platelet-Derived Extracellular Vesicles Alleviate Psoriatic Inflammation via Mitochondrial Transfer to Macrophages.

Abstract

Platelet-rich plasma (PRP) is a safe, autologous plasma component abundant in cytokines and extracellular vesicles, frequently applied to treat inflammatory disorders. Although PRP demonstrates potential for psoriasis therapy, its underlying mechanism remains insufficiently understood. In this study, various PRP constituents were evaluated in an imiquimod (IMQ)-induced mouse model of psoriasis. PRP, platelet-derived extracellular vesicles (PEVs), and platelet-poor plasma (PPP) were isolated from mice and administered subcutaneously. The data showed that PEVs, rather than PPP, served as the principal anti-psoriatic factor. Furthermore, RNA sequencing and flow cytometry revealed that PEVs markedly suppressed M1 polarisation of macrophages, thereby mitigating psoriatic-like inflammation. In vitro, PEVs delivered encapsulated mitochondria to RAW264.7 cells in a concentration-dependent manner. These functional organelles enhanced oxidative phosphorylation and suppressed glycolysis, driving a metabolic shift favouring an anti-inflammatory phenotype and attenuating the inflammatory response. In conclusion, PEVs emerge as the primary PRP component responsible for inflammatory suppression in psoriasis. Notably, mitochondria transfer mediated by PEVs underscores a promising therapeutic avenue and provides novel insight into the role of platelet derivatives in inflammatory diseases.