Ox40-Cre-Mediated Deletion of BRD4 Reveals an Unexpected Phenotype of Hair Follicle Stem Cells in Alopecia

The study reveals that BRD4 is essential for maintaining hair follicle integrity and preventing alopecia by investigating its role in OX40-expressing cells in mice. Conditional deletion of Brd4 in these cells led to alopecia, severe dermatitis, and significant skin pathology, including epidermal hyperplasia, hyperkeratosis, and loss of hair follicles. Lineage-tracing studies showed that OX40 is expressed by hair follicle stem cells (HFSCs), and BRD4 deletion in HFSCs disrupted follicle structures and blocked hair regeneration. RNA-Seq analysis indicated downregulation of SHH, cell cycle, and Wnt signaling pathways in BRD4-deleted HFSCs. Additionally, elevated levels of IL-17 and IFN-γ from γδ T cells contributed to skin inflammation, and BRD4 deletion in Tregs impaired their suppressive functions, exacerbating the condition. The findings underscore BRD4's critical role in HFSC proliferation, survival, and immune regulation in the skin.