High-resolution transcriptomic atlas of inflammatory skin diseases

Summary: Abstract Body: Atopic dermatitis (AD), psoriasis (PSO), hidradenitis suppurativa (HS) and vitiligo (VIT) are inflammatory skin diseases with distinct immunophenotypes. As we hypothesized that these diseases may share immunopathomechanisms for targeted therapeutics, we aimed to profile and identify the shared pathogenic loop as well as the unique molecular mechanisms of each disease. An atlas of over one million cells was generated by conducting single-cell RNA sequencing (scRNAseq) on lesional tissue biopsies and peripheral blood mononuclear cells (PBMCs) from approximately 80 patients. We report the immune signatures of each disease in both the active lesion and circulation. For keratinocytes (KC), the frequency of proliferating KC increased in both types of PSO, plaque and pustular, while that of basal KC was decreased in AD and PSO compared to control or VIT lesions. In AD lesions, T helper type (Th) 2 and Th22 responses were elevated, while in PSO lesions, Th1 and Th17 responses were upregulated. In the circulation of HS patients, Th1, Th2, Th17 and Th22 responses were elevated suggesting its complex immune response. Other disease-specific signatures in immune cell subsets were explored, including regulatory T cells, which were elevated in the circulation of AD patients, and macrophages, which were elevated in PSO lesions. We validated our findings at the protein level using multiplex immunofluorescent imaging (MACSima) and plan to validate using mass cytometry. In addition, a comprehensive spatial atlas is simultaneously being constructed using spatial transcriptomics profiling with a customized skin panel (Xenium). These integrated approaches aim to identify unique molecular mechanisms of inflammatory skin diseases, offering insights for the development of personalized treatment strategies and prediction of treatment response. Soyoung Jeong¹, Sowon Choi¹, Yewon Moon¹, Christine Suh-Yun Joh¹, Hyo Jeong Nam¹, Jung Ho Lee¹, Hyun Je Kim^{1, 2, 3} 1. Seoul National University Graduate School Department of Biomedical Science, Seoul, Korea (the Republic of). 2. Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Korea (the Republic of). 3. Department of Dermatology, Seoul National University Hospital, Seoul, Korea (the Republic of). Bioinformatics, Computational Biology, and Imaging