Macrophages induce AKT/β-catenin-dependent Lgr5+ stem cell activation and hair follicle regeneration through TNF
Skin stem cells can regenerate epidermal appendages; however, hair follicles (HF) lost as a result of injury are barely regenerated. Here we show that macrophages in wounds activate HF stem cells, leading to telogen-anagen transition (TAT) around the wound and de novo HF regeneration, mostly through TNF signalling. Both TNF knockout and overexpression attenuate HF neogenesis in wounds, suggesting dose-dependent induction of HF neogenesis by TNF, which is consistent with TNF-induced AKT signalling in epidermal stem cells in vitro. TNF-induced β-catenin accumulation is dependent on AKT but not Wnt signalling. Inhibition of PI3K/AKT blocks depilation-induced HF TAT. Notably, Pten loss in Lgr5+ HF stem cells results in HF TAT independent of injury and promotes HF neogenesis after wounding. Thus, our results suggest that macrophage-TNF-induced AKT/β-catenin signalling in Lgr5+ HF stem cells has a crucial role in promoting HF cycling and neogenesis after wounding.
Authors: Wang X1,2, Chen H2,3,4, Tian R2,5, Zhang Y6, Drutskaya MS7, Wang C1,2, Ge J1,2, Fan Z1,2, Kong D1,2, Wang X1,2, Cai T1,2, Zhou Y1,2, Wang J1,2, Wang J1,2, Wang S1,2, Qin Z8, Jia H9, Wu Y9, Liu J10, Nedospasov SA7, Tredget EE11, Lin M2, Liu J12, Jiang Y4, Wu Y2,3.
Influence Factor: 12.123
Citation: Nature Communications 8, 14091 (2017).