Spatial transcriptomics of hidradenitis suppurativa lesions informs key cell-cell communication networks between histological features

Summary: Abstract Body: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by abscesses, draining tunnels, and fibrotic scars, most often occurring in intertriginous areas. HS pathogenesis involves follicular occlusion and rupture, followed by complex interactions between keratinocytes, immune cells, and fibroblasts that drive lesion development. To investigate these cellular interactions within HS lesions, we used spatial transcriptomics (10x Genomics Visium platform) to map gene expression to histologic features in lesional tissue from four patients with severe axillary HS (Hurley stage III). Fresh-frozen samples of HS tissue were selected for spatial transcriptomics due to superior RNA quality compared to FFPE blocks. Samples showed histopathological features characteristic of severe HS including epidermal hyperplasia, plasmocytic infiltrate, cystic structures, and epithelialized tunnels. Compared to keratinocytes in the epidermis, tunnel and cyst keratinocytes showed enrichment of gene ontology terms involved in adaptive immunity. These dermal epithelial features were also marked by increased expression of B cell marker genes (e.g., MZB1, JCHAIN, IGHG3) in the surrounding tissue. Cell-cell communication analysis of the interplay between keratinocyte features, fibroblasts, and immune cells showed significant activation of chemokine signaling. Across multiple samples, CXCR4/CXCL12 signaling between the stroma and immune cells was the most significantly activated pathway. This pathway is a known mediator of inflammation as CXCL12 leads to chemotaxis of CXCR4 positive immune cells. Most of the immune infiltrate surrounding tunnels and follicular structures expressed CXCR4, while the region of the stroma immediately adjacent to these epithelial structures additionally expressed CXCL12. Our results indicate that the CXCL12/CXCR4 axis likely plays a role in the recruitment of B cell populations to dermal epithelial structures in HS. Austin B. Montgomery¹, Mackenzie L. Sennett¹, Amanda M. Nelson¹ 1. Dermatology, Penn State College of Medicine, Hershey, PA, United States. Bioinformatics, Computational Biology, and Imaging