Macrophages Promote Wound-Induced Hair Follicle Regeneration in a CXCR1- and TGF-β1-Dependent Manner.

Hair follicle stem cells are regulated by intrafollicular and extrafollicular niche signals. Appropriate hair follicle regeneration relies on the coordinated release and integration of these signals. How immune cells, particularly cutaneous macrophages, influence the hair follicle stem cell niche and regeneration is not well understood. We took advantage of wound-induced hair growth (WIHG) to explore the relationship between wound macrophages and hair follicle regeneration. First, we showed that WIHG is dependent on CD11bF4/80 macrophages at 7-11 days after injury. Next, using CXCR1:CCR2 mice to capture the dynamic spectrum of macrophage phenotypes during wound healing, we showed that wound macrophages transition from a CXCR1 to a CXCR1 phenotype at the onset of WIHG. Finally, WIHG is abolished in mice deficient for CXCR1, delayed with pharmacological inhibition of transforming growth factor-β receptor type 1, and rescued with exogenous transforming growth factor-β1. Overall, we propose a model in which transforming growth factor-β1 and CXCR1 are critical for recruiting and maintaining the CCR2CXCR1Ly6CTNFα macrophages critical for stimulating WIHG.