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.