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

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 beta 3 (TGF-beta 3), 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-beta 3 axis, highlighting a possible means of manipulating T-reg cells to support tissue regeneration. Skin T-reg cell crosstalk with hair-follicle stem cells (HFSCs) can control hair regrowth. Here the authors show that glucocorticoid receptor signaling in skin T-reg cells induces TGF-beta 3, which in turn facilitates HFSC proliferation.

Automated summary

This study reveals the interaction between T-reg cells and HFSCs, which is mediated by the glucocorticoid receptor signaling pathway and TGF-beta 3, promoting HFSC proliferation and skin regeneration.