Macrophages contribute to the cyclic activation of adult hair follicle stem cells

PLoS Biol. 2014 Dec 23;12(12):e1002002. doi: 10.1371/journal.pbio.1002002. eCollection 2014 Dec.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult Stem Cells / cytology*
  • Adult Stem Cells / metabolism
  • Animals
  • Apoptosis
  • Cell Count
  • Cell Cycle
  • Cell Differentiation
  • Female
  • Hair Follicle / cytology*
  • Hair Follicle / growth & development
  • Inflammation / pathology
  • Macrophages / cytology*
  • Macrophages / metabolism
  • Mice
  • Skin / pathology
  • Wnt Signaling Pathway

Grant support

DC is a recipient of a Spanish Association Against Cancer (AECC) postdoctoral fellowship. This work was supported by grants to MPM from the Spanish Ministry of Science and Innovation (BFU2009-11885 and BFU2012-33910). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.