Glucocorticoid signaling and regulatory T cells cooperate to maintain the hair-follicle stem-cell niche

Abstract

Maintenance of tissue homeostasis is dependent on the communication between stem cells and supporting cells in the same niche. Regulatory T cells (T_reg cells) are emerging as a critical component of the stem-cell niche for supporting their differentiation. How T_reg cells sense dynamic signals in this microenvironment and communicate with stem cells is mostly unknown. In the present study, by using hair follicles (HFs) to study T_reg cell-stem cell crosstalk, we show an unrecognized function of the steroid hormone glucocorticoid in instructing skin-resident T_reg cells to facilitate HF stem-cell (HFSC) activation and HF regeneration. Ablation of the glucocorticoid receptor (GR) in T_reg cells blocks hair regeneration without affecting immune homeostasis. Mechanistically, GR and Foxp3 cooperate in T_reg cells to induce transforming growth factor β3 (TGF-β3), which activates Smad2/3 in HFSCs and facilitates HFSC proliferation. The present study identifies crosstalk between T_reg cells and HFSCs mediated by the GR-TGF-β3 axis, highlighting a possible means of manipulating T_reg cells to support tissue regeneration.