Hair follicles undergo recurrent growth, regression, and resting phases throughout the postnatal life, which is supported by hair follicle stem cells (HFSCs). The niche components of HFSCs are important to maintain their quiescence and stemness. Gasdermin A3 (Gsdma3) gain-of-function mutations in mouse cause chronic skin inflammation, aberrant hair cycle, and progressive hair loss, which is similar to scarring alopecia seen in humans. However, the mechanism underlying these defects remains elusive. Here, we used a combined Cre/loxP and rtTA/TRE system to study the spatiotemporal effect of Gsdma3 overexpression on distinct stages in the hair cycle. We found that Gsdma3-mediated cell death affects anagen initiation, anagen progression, and catagen-telogen transition. Induced Gsdma3 expression causes the collapse of HFSC niche and precocious HFSC activation, leading to subsequent HF degeneration. Although macrophages and dendritic cells are recruited to the bulge region, suppression of the skin inflammation using topical immunosuppressants does not alleviate the cell death in the bulge. Our data exclude an immune-mediated mechanism for the pathogenesis of hair loss and suggest that activated Gsdma3 executed cell necrosis to induce club hair shedding and immediate anagen re-entry without going through telogen, with implication for Gsdma3 in HFSC niche maintenance.
Date:
2019-05
Relation:
Journal of Investigative Dermatology. 2019 May;139(5):S152.
