Analysis Identifies Distinct Keratinocyte and Fibroblast Niches in Severe HS

Researchers identified a pathogenic keratinocyte state and spatially distinct fibroblast populations in severe hidradenitis suppurativa (HS), providing new insights into epithelial–stromal and immune cell interactions that may contribute to disease persistence.

The study authors, publishing in the Journal of Investigative Dermatology, used single-cell RNA sequencing and spatial transcriptomics to characterize the cellular and molecular landscape of lesional skin from patients with severe HS, with particular emphasis on fibroblast–keratinocyte interactions.

Distinct Cellular Niches Identified in Severe HS Lesions

Investigators identified a migratory S100+ pathogenic keratinocyte state enriched in HS lesions, along with fibroblast populations occupying distinct tissue compartments. COL6A5+ papillary fibroblasts demonstrated spatial associations with undifferentiated keratinocyte populations and predicted fibroblast–keratinocyte communication networks. APOD+ fibroblasts were associated with immune-rich regions containing activated B cells and plasma cells, consistent with tertiary lymphoid organ (TLO)-like immune aggregates. Further analyses predicted extensive interactions between fibroblasts and both keratinocyte and immune cell populations.

The authors said the findings support a model of severe HS characterized by distinct epithelial and inflammatory stromal niches that may contribute to persistent disease. The authors also proposed that interactions among these cellular compartments may help explain the limited efficacy of therapies targeting individual inflammatory pathways.

Source

Du-Harpur X, et al. Journal of Investigative Dermatology. October 2026. Doi:10.1016/j.jid.2026.08.033