1619 Spatial transcriptomic analysis of imiquimod-treated mouse skin reveals deregulation of lipid raft-associated markers which could be reversed by re-introduction of caveolin scaffolding domain peptide

We have previously identified that a structural membrane protein caveolin-1 (Cav1) is involved in regulation of aberrant keratinocyte proliferation and differentiation, thus the aim this study was to elucidate role Cav1 pathogenesis psoriasis vulgaris. utilized spatial transcriptomic analysis combined with immunohistochemistry (IHC) patient samples mouse models. Omics analyses caveolae their components as downregulated imiquimod (IMQ)-treated model psoriasis. These observations were validated (n=21) multiple types (guttate, inverse, nail, palmoplantar, plaque, pustular) by IHC staining quantified QuPath image software. Although all biopsy exhibited an inverse relationship levels Cav1, plaque pustular most pronounced. To assess whether reintroduction can alleviate some features associated IMQ-induced (increased skin thickness/scaling upregulation markers), C57BL6 K14cre-Cav1 knockout mice treated soluble caveolin scaffolding domain (CSD) peptide, presence or absence IMQ. observed Cav1ko increased thickness expression CD11b, CD14, IL-6, IL-12, IL-17a TNFa, although lesser than IMQ-treated mice. Moreover, topical CSD treatment decreased both scaling, well dampened aforementioned inflammatory markers. Together, these data support hypothesis pathophysiological target introduce different approach localized targeting specialized microdomains, such caveolae.