833 Reintroduction of caveolin-1 scaffolding domain improves pathogenesis of psoriasiform dermatitis

Psoriasis is a chronic, inflammatory skin disease characterized by well-defined, erythematous plaques with silvery scale secondary to aberrant keratinocyte proliferation. We have previously identified that structural membrane protein caveolin-1 (Cav1) involved in regulation of proliferation and differentiation, thus the aim this study was elucidate role Cav1 pathogenesis psoriasis vulgaris. utilized spatial genomic & proteomic analyses combined immunohistochemistry (IHC) patient samples mouse models. Omics caveolae their components (Cav1, -2 cavin-1) as downregulated imiquimod (IMQ)-treated model psoriasis. These observations were validated multiple types stratified PASI score (plaque, inverse, guttate nail) IHC staining quantified QuPath image analysis software. Although all biopsy exhibited an inverse relationship levels Cav1, plaque most pronounced. To assess whether reintroduction can alleviate some features associated IMQ-induced (increased thickness/scaling upregulation markers), C57BL6 K14cre-Cav1 knockout mice treated soluble caveolin scaffolding domain (CSD) peptide, presence or absence IMQ. observed Cav1ko trend increased thickness expression CD11b, CD14, IL-6, IL-12, IL-17a TNFa, although lesser than IMQ-treated (Cav1 wild type). Moreover, topical CSD treatment decreased both scaling, well dampened aforementioned markers. Together, these data support hypothesis major pathophysiological target introduce different approach localized targeting specialized microdomains, such caveolae.