Macrophages Contribute to the Cyclic Activation of Adult Hair Follicle Stem Cells

TLDR

Skin epithelial stem cells depend on a complex signaling environment for regeneration, yet the influence of immune cells on these cells remains unclear. We found that macrophage apoptosis precedes hair follicle stem cell activation, that Wnt signaling mediates this effect, and that blocking macrophage‑derived Wnt delays hair growth, demonstrating that perifollicular macrophages are a novel cue for stem cell activation with potential therapeutic relevance.

Abstract

Skin epithelial stem cells operate within a complex signaling milieu that orchestrates their lifetime regenerative properties. The question of whether and how immune cells impact on these stem cells within their niche is not well understood. Here we show that skin-resident macrophages decrease in number because of apoptosis before the onset of epithelial hair follicle stem cell activation during the murine hair cycle. This process is linked to distinct gene expression, including Wnt transcription. Interestingly, by mimicking this event through the selective induction of macrophage apoptosis in early telogen, we identify a novel involvement of macrophages in stem cell activation in vivo. Importantly, the macrophage-specific pharmacological inhibition of Wnt production delays hair follicle growth. Thus, perifollicular macrophages contribute to the activation of skin epithelial stem cells as a novel, additional cue that regulates their regenerative activity. This finding may have translational implications for skin repair, inflammatory skin diseases and cancer.