1. Positionally distinct interferon stimulated dermal immune acting fibroblasts promote neutrophil recruitment in Sweet's syndrome.
- Author
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Cavagnero KJ, Albright J, Li F, Dokoshi T, Bogle R, Kirma J, Kahlenberg JM, Billi AC, Fox J, Coon A, Dobry CJ, Hinds B, Tsoi LC, Harms PW, Gudjonsson JE, and Gallo RL
- Abstract
Sweet's syndrome is a poorly understood inflammatory skin disease characterized by neutrophil infiltration to the dermis. Single-nucleus and bulk transcriptomics of archival clinical samples of Sweet's syndrome revealed a prominent interferon signature in Sweet's syndrome skin that was reduced in tissue from other neutrophilic dermatoses. This signature was observed in different subsets of cells, including fibroblasts that expressed interferon-induced genes. Functionally, this response was supported by analysis of cultured primary human dermal fibroblasts that were observed to highly express neutrophil chemokines in response to activation by type I interferon. Furthermore, single-molecule resolution spatial transcriptomics of skin in Sweet's syndrome identified positionally distinct immune acting fibroblasts that included a CXCL1+ subset proximal to neutrophils and a CXCL12+ subset distal to the neutrophilic infiltrate. This study defines the cellular landscape of neutrophilic dermatoses and suggests dermal immune acting fibroblasts play a role in the pathogenesis of Sweet's syndrome through recognition of type I interferons., Competing Interests: Conflict-of-interest statement: RLG is a consultant for and has equity interest in MatriSys bioscience and Sente Inc.
- Published
- 2024
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