Immune signatures of megakaryocytes in persistent inflammation-immunosuppression and catabolism syndrome

• Single-cell RNA sequencing identifies five distinct megakaryocyte (MK) subsets (MK1–MK5) in peripheral blood, with MK1 and MK2 predominant in PICS patients. • MK1 shows enrichment in antigen processing/presentation and IL-17 signaling, while MK2 is associated with platelet degranulation and neutrophil activation, indicating functional specialization. • CCL5 expression is markedly upregulated in MKs, and ligand-receptor analysis reveals dynamic interactions with various immune cells, suggesting a broad immunoregulatory role. • In a PICS mouse model, MKs reduce systemic inflammation by lowering TNF-α and IL-17A levels and promote lung tissue repair, highlighting their potential as therapeutic targets for post-sepsis immune dysfunction.