Single cell and spatial sequencing define processes by which keratinocytes and fibroblasts amplify inflammatory responses in psoriasis

Abstract The immunopathogenesis of psoriasis, a common chronic inflammatory disease of the skin, is incompletely understood. Here we demonstrate, using a combination of single cell and spatial RNA sequencing, IL-36 dependent amplification of IL-17A and TNF inflammatory responses in the absence of neutrophil proteases, which primarily occur within the supraspinous layer of the psoriatic epidermis. We further show that a subset of SFRP2 + fibroblasts in psoriasis contribute to amplification of the immune network through transition to a pro-inflammatory state. The SFRP2 + fibroblast communication network involves production of CCL13 , CCL19 and CXCL12 , connected by ligand-receptor interactions to other spatially…

• NS
  National Science Foundation
• DF
  Dermatology Foundation
• NP
  National Psoriasis Foundation
• AA
  A. Alfred Taubman Medical Research Institute
• NR
  National Research Foundation
• SN
  Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung

  Award: 310030B_182834