A peripheral glial niche orchestrates the early stages of skin wound healing

Skin repair is a complex, dynamic process involving multiple cell types. Using multiplex imaging, spatial transcriptomics, and single-cell RNA sequencing, we show that peripheral nerves—containing repair glia—form a pro-reparative niche closely interacting with macrophages and proliferating fibroblasts in acute skin wounds. Repair glia function as critical early-stage regulators of wound healing by initiating the inflammatory response through secretion of monocyte chemoattractant proteins, such as CCL2, which recruit monocyte-derived macrophages. Accordingly, depletion of repair glia as well as glia-specific deletion of CCL2 reduces the number of macrophages, leading to impaired fibroblast proliferation and diminished fibroblast-to-myofibroblast transition. These findings identify repair glia as early regulators of the immune response, orchestrating the spatiotemporal progression of wound healing. • In acute skin wounds, a pro-reparative niche forms around nerves containing repair glia • Repair glia regulate macrophage recruitment via monocyte chemoattractant proteins • Macrophages influence fibroblast proliferation and transition into myofibroblasts • Glia depletion affects the key stages of wound repair Repair glia in peripheral nerves are part of a regenerative niche in acute skin wounds. This glial niche promotes skin wound healing by regulating innate immune cell recruitment, in particular monocytes and monocyte-derived macrophages, both critical for a successful repair process.