A macrophage-induced subpopulation of mesenchymal cells expressing Fcer1g contributes to wound-induced fibrosis.

Fibrosis commonly occurs during adult skin wound healing, characterized by excessive extracellular matrix (ECM), leading to scarring. Mesenchymal cells, the primary ECM-producing population, are heterogeneous with varying fibrotic propensity during healing. While pro-fibrotic embryonically derived mesenchymal lineages have been identified, adult mesenchymal cells responsible for fibrosis are not yet fully characterized. In adult mice with conditional macrophage depletion during the early phase of wound healing, wounds exhibit attenuated fibrosis and a reduction in mesenchymal cell numbers. Here we show that early phase macrophage induces a distinct PDGFRα⁺ mesenchymal population expressing Fcer1g. This cell population expands rapidly after injury, shows high proliferative activity, and is largely absent when macrophages are depleted. Targeted ablation of this cell population does not delay wound closure but results in diminished scarring. Human wound datasets identified a transcriptionally conserved FCER1G-expressing mesenchymal subset, suggesting that this pro-fibrotic mesenchymal state is preserved in human wound healing.

Duke Scholars

Author Benjamin Aaron Alman Orthopaedic Surgery