Epidermal keratinocytes in hidradenitis supprativa fistulas and pyoderma gangrenosum lesions are similarly innate-immunologically activated

Summary: Abstract Body: Hidradenitis suppurativa (HS) is a neutrophilic dermatosis that typically arises after puberty, presenting with characteristic skin lesions such as inflammatory nodules and painful abscesses primarily in the axillae and groin. These lesions originate from the hair follicles and are driven by follicular obstruction, cyst formation, and rupture, triggering acute inflammation. Pyoderma gangrenosum (PG) is also a neutrophilic dermatosis that begins after minor trauma with painful erythema, folliculitis-like nodules, blisters, and pustules, which quickly ulcerate and expand. Neutrophils play an important role in the pathology of these diseases, and epidermal keratinocytes are also thought to be involved in the pathology, but there have been no detailed analyses of this point. Here, we focused on the keratinocytes in these lesions and performed spatial transcriptome analysis using GeoMx. Regions of interest (ROIs) were selected from the keratinocytes in the fistula areas of HS, the lesional epidermis of PG, and normal epidermis. Transcriptomic comparisons revealed that neutrophil-associated and immune-related pathways were activated in both HS fistula and PG lesional epidermis. Specific genes, including CXCL1, S100A8, S100A9, and DEFB4B, showed elevated expression in both conditions, highlighting shared molecular mechanisms. Additionally, in HS fistula epidermis, increased expression of B cell-related genes was observed, suggesting a potential role for B cells in local immune responses and inflammation regulation. These findings demonstrate that HS and PG share a molecular basis as neutrophilic dermatoses and provide insights into the pathogenesis of these conditions. This study contributes to the understanding of HS and PG and may guide the development of novel therapeutic strategies. Kenichi Hasui¹, Yoshio Kawakami¹, Yoshihiro Matsuda¹, Himino Ashida¹, Yohei Yasutomi¹, Shuta Tomida², Shin Morizane¹ 1. Dermatology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama, Japan. 2. Center for Comprehensive Genomic Medicine, Okayama University Hospital, Okayama, Japan. Adaptive and Auto-Immunity