scRNA-Seq of human skin reveals IL-17–mediated CXCL12+ dermal fibroblast – neutrophil communication in psoriasis. (A–K) Analysis of scRNA-Seq of skin from psoriasis patients (N = 3) and healthy controls (N = 3). (A) Dimensionality reduction is split by condition and colored by cell type. (B) Network analysis showing communication toward myeloid cells (left) and from fibroblasts (right). Edge weight is proportional to communication strength. Edge and node color indicates communication source. (C) GSEA of fibroblasts using KEGG database. (D) Expression of neutrophil chemokines across cell types. (E) Dimensionality reduction of fibroblast subset colored by cluster. Dashed line separates FB1–FB6 and FB7–FB11. (F) Expression of fibroblast subset marker genes across clusters. Boxes highlight high expression of reticular and adipocyte lineage genes in FB1–FB6 and high expression of papillary and myofibroblast genes in FB7–FB11. (G) GO term analysis comparing FB1–FB6 and FB7–FB11. (H) Network analysis showing communication from FB1–FB6 and FB7–FB11 toward neutrophils and other myeloid cells. (I) Neutrophil chemokine expression across fibroblast clusters. (J) DEGs between neutrophil chemokine+/− fibroblasts in psoriasis using Wilcoxon Rank Sum test. Log₂ fold-change and P value (adjusted) cut-offs are 0.5 and 0.05, respectively. (K) Expression of neutrophil chemokine+/− fibroblast markers in psoriasis. (L) Expression of genes associated with fibroblast–neutrophil communication by bulk RNA-Seq in human psoriasis patients on and off anti–IL-17A treatment, scaled by row. Averages shown for N = 8–10. (M) Representative CXCL1 and CXCL12 immunostaining in lesional skin from psoriasis patients untreated and treated with anti–IL-17A. Scale bar, 300 μm.