1054 Circulating inflammatory monocytes associated with atopic dermatitis microbial-defined endotypes

Previously, we examined the prognostic utility of skin microbiome-based stratification for atopic dermatitis (AD) and defined steady-state microbial configurations (“dermotypes”) that classified patients by clinical severity, cutaneous barrier properties IgE status. Here, explored circulating immune dysregulation underlying microbiome-stratified AD to elucidate heterogeneity in profiles. Using single-cell profiling PBMCs, observed cell heterogeneity, characterized enrichment late inflammatory monocytes associated with dermotype B subjects compared A healthy controls. These were mainly classical CD14+ expressing proinflammatory alarmins S100A8, S100A12, S100A9 chemokines such as CCL3 CCL4. Further validation using high-dimensional flow detected concomitant upregulation genes, IL-1B TNF-a, could exacerbate inflammation patients. Interestingly proportions atopy-relevant types, Th2, Th2a NK, did not differentiate based on or alone, however, ILC3 significantly reduced A. The role is unclear, previous reports show limit Type 2 asthma. We then investigated circulatory cytokine levels blood plasma cytokines monocyte-related proteins (TRAIL, TRANCE, MCP4 IL-18) B. This validates scRNA-seq findings monocyte-driven inflammation. Our results confirm a pathophysiological microbiome-defined subgroup identified cellular basis increased exacerbated host linked dermotypes.