Gsdma3 Mutation Causes Bulge Stem Cell Depletion and Alopecia Mediated by Skin Inflammation

The study examined the effects of a Gsdma3 mutation in AE mice, which led to progressive alopecia due to the depletion of bulge stem cells in hair follicles, mediated by skin inflammation. AE mice experienced complete hair loss by 6 months, with histological analysis showing hyperkeratosis, catagen delay, and a severe inflammatory condition characterized by elevated tumor necrosis factor-α and increased immune cells. The immune privilege in the bulge was compromised, leading to stem cell destruction. Treatment with cyclosporine A improved the condition by reducing inflammation, highlighting the role of immune-mediated destruction in the pathogenesis of alopecia. The AE strain served as a model for primary cicatricial alopecias, such as lichen planopilaris.