IL10 promotes surgical incision healing in sepsis by regulating PI16+ fibroblasts and CCL8+ macrophages.

Sepsis severely impairs surgical incision healing, but the underlying mechanisms and effective interventions remain insufficiently understood. Interleukin-10 (IL10) exerts potent anti-inflammatory activity, yet its role in regulating fibroblast and macrophage dynamics during septic wound repair is unclear. Human peri-incisional skin specimens were collected from septic and non-septic patients. A lipopolysaccharide (LPS)-induced sepsis mouse model with surgical incision was established, followed by IL10 treatment. Single-cell RNA sequencing, cell trajectory analysis, cell-cell communication analysis, gene set variation analysis, and immunofluorescence were used to investigate cellular and molecular alterations. Only mouse samples were used for single-cell sequencing in this study. Single-cell analysis identified 8 cell types, including 3 non-immune cell types and 5 immune cell types. Sepsis increased NK cells and macrophages, and upregulated PI16⁺ fibroblasts and CCL8⁺ macrophages in wound tissue. IL10 treatment elevated mast cells, T cells, and neutrophils, downregulated peptidase inhibitor 16 (Pi16) and chemokine ligand 8 (Ccl8) expression, and attenuated fibroblast-macrophage crosstalk. Mechanistically, IL10 promoted fibroblast proliferation by inducing macrophages to secrete Il1b and Osm. Sepsis delays surgical incision healing via upregulating PI16⁺ fibroblasts and CCL8⁺ macrophages and enhancing inflammatory cell crosstalk. IL10 accelerates wound repair by suppressing these detrimental subsets and activating Il1b/Osm-mediated fibroblast proliferation. PI16 and CCL8 may serve as potential therapeutic targets for septic wound healing.