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- W4285984920 abstract "Hidradenitis suppurativa (HS) is a chronic, inflammatory skin disease characterized by a massive immune cell infiltrate, extensive fibrosis, and tissue destruction. We aimed to elucidate the role of fibroblasts in the pathophysiology of HS. Single-cell RNA-sequencing was performed on chronic lesional skin samples of 6 HS patients and skin samples of 7 controls. Spatial sequencing was performed on 4 HS skin samples. Fibroblast subclustering revealed 6 subsets (SFRP2+, COL11A+, SFRP4+, LSP1+, RAMP1+, and CXCL13+). Two of these, SFRP4+ and CXCL13+, were specifically derived from HS samples and displayed enhanced pro-fibrotic characteristics (increased COL1A1 and COL3A1 expression). Development and activation of these subsets were found to be driven by key HS-associated inflammatory cytokines (IFNγ, IL-1β, and TNF). IHC and spatial sequencing revealed that their location demarcates the inflammatory area in HS skin. Activated SFRP4+ and CXCL13+ FB subsets were shown to help coordinate the characteristic chronic infiltrate by attracting neutrophils and Th17 cells through the expression of chemokines including CXCL5, CXCL6, and CCL20. Furthermore, increased CXCL13 expression by the CXCL13+ subset likely facilitates migration of B cells to the inflammatory environment and formation of tertiary lymphoid structures located within the fibrotic zone surrounding the infiltrate. These findings demonstrate the role of distinct FB subsets, activated by key HS-associated cytokines, in shaping the immune cell composition and spatial architecture of HS." @default.
- W4285984920 created "2022-07-20" @default.
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- W4285984920 date "2022-08-01" @default.
- W4285984920 modified "2023-09-28" @default.
- W4285984920 title "804 Fibroblast subpopulations orchestrate chronic inflammation in hidradenitis suppurativa" @default.
- W4285984920 doi "https://doi.org/10.1016/j.jid.2022.05.818" @default.
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