Thymic stromal lymphopoietin controls hair growth

Highlights

• TSLP is produced in the skin in response to injury and during hair follicle cycling.

• LGR5⁺ stem cells and progeny in the hair follicle respond to TSLP.

• Targeted deletion of Tslpr on LGR5⁺ HFSCs delays wound-induced hair growth.

• TSLP mediates cyclin D1 and DDX6 upregulation and drives keratinocyte proliferation.

Summary

Skin tissue regeneration after injury involves the production and integration of signals by stem cells residing in hair follicles (HFSCs). Much remains unknown about how specific wound-derived factors modulate stem cell contribution to hair growth. We demonstrate that thymic stromal lymphopoietin (TSLP) is produced in response to skin injury and during the anagen phase of the hair cycle. Intradermal injection of TSLP promoted wound-induced hair growth (WIHG), whereas neutralizing TSLP receptor (TSLPR) inhibited WIHG. Using flow cytometry and fluorescent immunostaining, we found that TSLP promoted proliferation of transit-amplifying cells. Lgr5^CreER-mediated deletion of Tslpr in HFSCs inhibited both wound-induced and exogenous TSLP-induced hair growth. Our data highlight a novel function for TSLP in regulation of hair follicle activity during homeostasis and wound healing.