373 Identification of immune cell pathways in acne vs. rosacea by single-cell RNA sequencing and single-cell spatial imaging

Acne and rosacea are both highly prevalent inflammatory skin diseases that characterized by erythema, papules, pustules, primarily involving the pilosebaceous units of face, yet with distinct mechanisms disease pathogenesis. Here, we used single-cell RNA-sequencing (scRNA-seq, n=22) spatial imaging (CosMx, n=4) to compare gene expression individual cells in acne vs. lesions elucidate pathways proximity unit. Surprisingly, found using scRNA-seq immune cell compositions were similar, composed Th17 TREM2 macrophages. We previously macrophages derived vitro treatment major sebum lipid squalene unable mount an antimicrobial response via induction reactive oxygen intermediates against Cutibacterium acnes, commensal contributes pathogenesis acne. Further, C. acnes antigens readily detected immunohistochemistry lesions. Across all types lesions, there 155 genes upregulated Of lesion signature genes, 65 corresponded a keratinocyte (KC) subcluster representing inflamed spinous KC. 37 involved including six S100 family members, CCL20, DEFB1, IL18, SLPI, SPINK5, SOD2. These colocalized CosMx In summary, express KC includes 37-gene program potential limit bacterial colonization but given many these pro-inflammatory, also contribute inflammation is typical clinical presentation