659 Persistence of mature dendritic cells, Th2A and Tc2 cells characterize clinically resolved atopic dermatitis under IL-4R-alpha blockade

Current therapeutic options for atopic dermatitis (AD) consist of either broad or targeted immunosuppressive agents. However, the natural course AD can hardly be modified, as disease invariably returns after cessation treatment. Tissue-resident memory T-cells are hypothesized to relevant players in mediating disease-specific ‘immune memory’, but their exact immunopathological phenotype is so far unknown. By using a multi-omics approach involving single-cell RNA sequencing combined with multiplex proteomics skin samples, we studied patients undergoing short (16 weeks) and long-term (one year) treatment IL-4Rα blocker dupilumab. blockade resulted clearance disease, decrease immune cell counts, normalization transcriptomic dysregulation keratinocytes. Interestingly, found distinct populations dendritic cells (DC) that were largely absent healthy control persist up one year These included LAMP3+ CCL22+ mature DC, CRTH2+ CD161+ Th2A cells, CRTAM+ cytotoxic T-cells, expressing peak levels CCL17 IL13 (T-cells). showed specific receptor constellation IL17RB, IL1RL1 (ST2) CRLF2, possibly rendering them key responders AD-typical epidermal alarmins IL25, IL33 TSLP. We thus identified persisting DC maintained an inflammatory treatment,equipped all receptors facilitate keratinocyte-DC-Th2-mediated response. emerge central skin-intrinsic leads recurrences, might therefore promising targets achieve more sustained