Immune microenvironment and fibroblast subpopulation in diabetic wound healing.

Diabetic foot ulcer (DFU) presents a major clinical challenge due to impaired healing mechanisms. Through the single-cell RNA sequencing of granulation tissue during wound repair, we identified distinct cellular alterations in DFU. Our analysis revealed an inflammatory monocyte axis involving CD14 (+) CCL2 (+) and FCN1 (+) CCR2 (+) subpopulations, coupled with an imbalance between diminished IL2RA (+) FOXP3 (+) regulatory T cells and expanded CD8 (+) GZMK (+) effector T cells. Fibroblast analysis showed a selective reduction in COL6A1 (+) COL6A3 (+) and COL7A1 (+) COL10A1 (+) subpopulations. Fluorescence imaging confirmed these transcriptional changes at the protein level. This comprehensive profiling of the DFU repair microenvironment uncovers specific immune-fibroblast interactions that may underlie healing impairment, offering new directions for targeted therapeutic development.