Early versus late hidradenitis suppurativa: Type 17 T-cell and B-cell inflammation precedes dermal tunnel and tertiary lymphoid structure formation

Hidradenitis suppurativa (HS) is a debilitating inflammatory skin disease that progresses from superficial nodules in early stages to deep dermal tunnels, tertiary lymphoid structures (TLSs), and fibrosis in later stages. Interplays between dermal tunnel keratinocytes, TLSs, and fibroblasts promote pathogenic T-cell and B-cell inflammation in late-stage disease. However, whether T-cell and B-cell inflammation sequentially precedes or follows the late-stage structure formation is unclear. The study aims to elucidate the sequence of inflammation from early- to late-stage HS by comparing their single-cell transcriptomes with those of psoriasis. We analyzed gene expression differences between early-stage HS and late-stage HS using single-cell RNA sequencing. The result showed plasma cell expansion, multifunctional B-cells expressing pro-inflammatory cytokines, major histocompatibility complex molecules, and immunoglobulins in HS. Unlike in late-stage HS, T-cells were the primary producers of the B-cell chemoattractant CXCL13 in early-stage HS. Overall design: Early-stage hidradenitis suppurativa (HS), late-stage HS, psoriasis lesional skin, and psoriasis non-lesional skin specimens were collected by skin biopsy procedures. All the human tissue specimens were collected with informed consent in accordance with the Declaration of Helsinki, and local ethics review boards approved the study. Collected skin tissues were incubated in culture medium for 48 hours. Emigrating cells from the skin tissues after 48-hour incubation were harvested and studied by droplet-based single-cell RNA sequencing.