922 Analysis of inflammatory pathways induced in dendritic cell-types by different strains of cutibacterium acnes: Lessons for acne therapy

Dendritic cells (DCs) are unique cell populations that link the innate and adaptive immune responses. However, how Cutibacterium acnes strains regulate DC function in acne remains unclear. We stimulated three DC cell-types [Langerhans cell-derived (LCDC), monocyte-derived (moDC), and myeloid (mDC)] with “healthy (CH)” or “acne (CA)” associated C. acnes strains and performed RNAseq to define DC immune signatures. Further, we conducted Differential Gene Expression (DEG) followed by Gene Set Enrichment Analysis (GSEA), Gene Ontology (GO) and pathway deconvolution. Gene expression analysis in DC cell-types exposed to C. acnes compared to the untreated controls revealed 4004 DEG in LCDC, 4438 in moDC and 5004 in mDC. GSEA identified unique genes and inflammatory pathways in acne, whereas, pathway deconvolution, demonstrated that LCDCs had the lowest response following C. acnes stimulation. Focusing on genes differentially expressed in each DC cell-type, we found 1301 genes exclusively upregulated after CA stimulation of LCDC, with GO analysis revealing genes involved in cytokine-cytokine receptor interactions, IL-17 and MAPK signaling. In moDC, we observed similar GO results with 19 uniquely upregulated genes. In mDC, we found 109 uniquely downregulated genes, including H2A, H4, PAD4, C5a, and PLC that are involved in extracellular trap formation pathways. Our findings support the hypothesis that C. acnes strains differentially regulate downstream DC functions. Future studies should focus on developing therapies that enhance DC function and abrogate the inflammatory pathways in acne.