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 <i>CD14</i> ⁺ <i>CCL2</i> ⁺ and <i>FCN1</i> ⁺ <i>CCR2</i> ⁺ subpopulations, coupled with an imbalance between diminished <i>IL2RA</i> ⁺ <i>FOXP3</i> ⁺ regulatory T cells and expanded <i>CD8</i> ⁺ <i>GZMK</i> ⁺ effector T cells. Fibroblast analysis showed a selective reduction in <i>COL6A1</i> ⁺ <i>COL6A3</i> ⁺ and <i>COL7A1</i> ⁺ <i>COL10A1</i> ⁺ 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.