Single cell analysis of hidradenitis suppurativa compared to Crohn’s disease

Summary: Abstract Body: Hidradenitis suppurativa (HS) and Crohn’s disease (CD) are chronic inflammatory disorders affecting distinct anatomical regions yet exhibiting shared phenotype. HS manifests as a skin condition characterized by the formation of deep abscesses and tunnel formation in intertriginous areas, while CD primarily affects the gastrointestinal tract. Despite clinical and immunological overlaps, the precise mechanisms driving fistula formation, a hallmark of both conditions, remain poorly understood. Here, we performed single-cell RNA sequencing (scRNA-seq) on inflamed skin biopsies from HS patients (n=16) and intestinal biopsies from CD patients (n=24) to delineate the common pathologic loop underlying fistula generation. Given the systemic nature of both diseases, we further generated scRNA-seq and mass cytometry profiling of peripheral blood mononuclear cells from HS (n=56) and CD (n=32) patients to elucidate the shared immune dysregulation within circulating immune cells. Building on our previous findings that implicate dysfunctional regulatory T cells (Tregs) in early-stage HS pathogenesis, we hypothesize that impaired Treg functionality similarly contributes to the immunopathology of CD. To further validate our findings, we used spatial transcriptomics at single-cell resolution, revealing shared pathogenic mechanisms of immune dysregulation and identifying potential therapeutic targets. Christine Suh-Yun Joh¹, Soyoung Jeong¹, Seong-Joon Koh², Young In Lee³, Hyun Je Kim^{1, 4} 1. Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Korea (the Republic of). 2. Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Jongno-gu, Seoul, Korea (the Republic of). 3. Department of Dermatology, Yonsei University College of Medicine, Seodaemun-gu, Seoul, Korea (the Republic of). 4. Department of Dermatology, Seoul National University Hospital, Jongno-gu, Seoul, Korea (the Republic of). Epidermal Structure and Barrier Function