730 Elevated levels of caveolin-1 in frontal fibrosing alopecia, central centrifugal cicatricial alopecia and lichen planopilaris suggests a conserved pathway in pathogenesis of scarring alopecia

Cicatricial alopecias (CAs) are a disfiguring and difficult to treat types of hair disorder that associated with distressing scalp symptoms significant secondary morbidity, marked psychological impact, loss quality life. The purpose our study was generate proof-of-principle for fundamentally innovative strategy treating CAs by therapeutically targeting caveolin-1 (Cav1), which is the principal structural component specialized membrane microdomains, using cholesterol depleting agents (cyclodextrins), in full length human ex vivo follicle (HF) organ culture mouse models. Our preliminary data suggest Cav1 preferentially localizes outer root sheath cells bulge HFs, houses epithelial stem (eHFSCs) required HF development, maintenance cyclic renewal, while overexpressed mislocalized lesional frontal fibrosing alopecia (FFA), central centrifugal cicatricial (CCCA) lichen planopilaris (LPP) (n=3). Moreover, localized topical application cyclodextrins (MβCD) downregulates expression bulge, similar knockout mice skin (inducible under K15 promoter), exhibits: 1) upregulation key guardians immune privilege (IP) (CD200 IL-10), 2) downregulation IP collapse-promoting signals (Substance P, β2MG, MHC Class I CXCL11), 3) E-cadherin. This strongly suggests previously unrecognized, clinically important involvement eHFSC function survival role overexpression CA pathobiology supports therapeutic as novel management strategy.