Spatial Transcriptomic Profiling Reveals the Pathophysiology of Early Stage Hidradenitis Suppurativa

Abstract

Abstract Hidradenitis suppurativa (HS) is a chronic inflammatory skin disorder that ranges from superficial nodules and deep abscesses to draining dermal tunnels in the intertriginous regions. It causes significant pain, scarring, and a poor quality of life, yet there are currently no effective treatment options. The role of tunnels or sinus tracts—a unique feature of moderate to severe HS—was reported that the epidermal tunnels are the source of inflammatory mediators in Hurley stages II and III. However, the pathophysiology of early stage HS needs further investigation. Here, we examined the intradermal epithelial cells surrounding these nodules in early HS in order to explore their features and function. Utilizing spatial transcriptomics, a cutting-edge technique that offers both spatial information of cells and their gene expression profiles, we compared the intradermal epithelial cell of HS patients in the early Hurley stage with the dermal wall of epidermal cysts in epidermal cyst patients. As expected, keratinocytes in the epidermis of individuals with HS were significantly activated, with increased levels of inflammatory cytokines, including IL-36G and CXCL8. In addition, the increase of IL-4R and IL-13RA1 suggests the increase of the sensitivity of Th2 cytokine on the epidermis and in dermal-infiltrating immune cells. Moreover, genes associated with B lymphocytes were highly expressed in the infiltrating immune cells of HS, implicating the importance of “epidermis-derived” inflammatory cytokines and the role of B cell infiltration in the pathomechanism of early HS.