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

Abstract

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.