Injury-induced hair growth response is promoted by tissue macrophages via insulin-like growth factor 1

Abstract Hair follicles (HFs) produce hair to mediate the first line of defense in mammals. HFs undergo cyclical production (anagen), and while this process is unsynchronized during adulthood, external cues, including shaving, induce synchronized anagen bolster surface barrier. Herein, we show that macrophages were crucial promoting anagen. Shaving triggered accumulation secondary germs (SHG), which underwent proliferation as early Day3 post-induction. Constitutive ablation markedly delayed anagen, targeted at Day 3, but not 0 or 6 post-shaving, impaired SHG activation with Anagen entry was dependent on Folr2 +tissue macrophages, CCR2 +monocyte-derived macrophages. Single-cell RNA-sequencing cell-cell communication analyses revealed +macrophages communicated SHGs via Igf1 (encoding insulin-like growth factor 1 IGF1). Ablation deletion IGF1 from decreased AKT signaling led both rescued injection recombinant vivo. ATAC-sequencing lack IGF1-from resulted alteration transcription motif enrichment chromatin accessibility various genes SHGs, demonstrating primed enter by IGF1R signaling. These results highlight importance immune-tissue crosstalk facilitating provide impetus for strategies promote growth.