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The interaction between fibroblasts and macrophages is already mature in vitro, and fibroblast-derived colony-stimulating factor 1 (CSF1) supports macrophages in some tissues. However, it is unclear whether macrophages regulate fibroblasts in vivo. Using genetic mouse models, single-cell omics, flow cytometry, and imaging techniques, we demonstrated that depletion of fibroblasts or loss of fibroblast-derived growth factors affects the skin macrophage population in the dermis and subcutaneous layer. Conditional deletion of Csf1 in Dpt+ fibroblasts gradually reduces CD64+ and CD11c+ macrophages, thereby impairing skin wound healing. Decreased macrophage abundance interferes with the regulation of fibroblast cell cycle, metabolism, and immune signal transduction, and increases fibroblast abundance, confirming the reciprocal relationship. In human systemic sclerosis (scleroderma), elevated CSF1 derived from fibroblasts and increased macrophage abundance are associated with disease severity, indicating that the CSF1-CSF1R axis is associated with the pathology. These findings provide in vivo evidence that macrophages regulate fibroblasts, revealing a bidirectional interaction, and advancing the understanding of tissue homeostasis and skin immune regulation.
This study was published in Nature Immunology under the title "Reciprocal regulation of fibroblast-macrophage equilibrium governs skin integrity".
Reference Information:
DOI: 10.1038/s41590-026-02434-5
