Peripheral nerve-derived CSF1 induces BMP2 expression in macrophages to promote nerve regeneration and wound healing.

The precise mechanisms regulating inflammatory and prorepair macrophages have not been fully elucidated, despite the pivotal role played by innate immunity in wound healing. We first employed a denervation wound model to validate the crosstalk between neurons and macrophages. Compared to normal wound healing, the denervation wound healing process involved fewer macrophages, decreased angiogenesis, and delayed wound healing. Consistent with the results of the scRNA-seq libraries, the number of early-phase wound proinflammatory and late-phase wound prorepair macrophages were decreased during the denervation wound healing process. We profiled early-phase and late-phase skin wounds in mice at the transcriptional and functional levels and compared them to those of normal wounds. We revealed a neuroimmune regulatory pathway driven by peripheral nerve-derived CSF1 that induces BMP2 expression in prorepair macrophages and enhances nerve regeneration. Crosstalk between neurons and macrophages facilitates the healing process of wounds and provides a potential strategy for wound healing therapy.