Integrated analysis reveals the unique protein composition of Th17 cell extracellular traps in acne vulgaris 2729

Abstract Description Extracellular traps (ETs), initially discovered in neutrophils, are now recognized in other immune cells, including T cells. Recent studies report antigen-specific T cells producing extracellular traps, but their protein composition and function remain poorly understood. Here, we induced ETs in human neutrophils (NETs) and Th17 cells (TETs) using different Cutibacterium acnes (C. acnes) phylotypes and employed integrated proteomics, transcriptomics, and acne biopsy analysis to characterize their protein composition and gene profiles. Principal component analysis and heatmaps revealed consistent protein profiles in NETs across C. acnes phylotypes, while TETs exhibited significant compositional shifts, highlighting distinct responses to different C. acnes phylotypes. Comparative analysis identified TET-specific proteins, including HLA-DRB5, TAP1, and GZMM, linked to bacterial disruption, T-cell activation, and antigen presentation. Shared proteins, such as H2BC21, HBD, and HMGN2, were associated with antimicrobial defense, anti-inflammatory regulation, and bacterial entrapment. Spatial RNA-seq analysis of acne biopsies further validated the distinct protein profiles in TETs. Insights into the role of skin microbes in regulating ET formation and release have broad implications for developing novel probiotics for acne and treating other inflammatory skin disorders. Funding Sources NIH R01AR081337 Topic Categories Microbial, Parasitic, and Fungal Immunology (MPF)