biostudies-literatureImanishi INational Center for Advancing Translational SciencesNCATS NIH HHSAmerican Skin AssociationNCI NIH HHSNational Institutes of HealthSociety for Investigative DermatologyNIAMS NIH HHSRegeneron Pharmaceuticals IncDamon Runyon Cancer Research FoundationNIH HHSIcahn School of Medicine at Mount Sinai116114https://www.ebi.ac.uk/biostudies/studies/S-EPMC12449769biostudies-literatureUnknown44(8)Chronic inflammatory skin diseases arise from dysregulated interactions between tissue-resident and infiltrating cells, the complexity of which hinders disease understanding and treatment. To address this, here, we present a single-cell spatiotemporal atlas of murine type 2 skin inflammation using MERFISH and scRNA-seq. Analyzing ∼430,000 cells during MC903- and oxazolone-induced dermatitis, we identify 39 cell types, including pro-inflammatory fibroblasts that resemble those in human atopic dermatitis. Spatial neighborhood analyses reveal basophils as potent activators of pro-inflammatory fibroblasts, with basophil-derived oncostatin-M (OSM) and IL-4 synergizing fibroblast-mediated feedforward basophil and immune recruitment. While fibroblast-specific deletion of the IL-4Rα receptor disruCell reportsA basophil-fibroblast pro-inflammatory axis fuels type 2 skin inflammation.PMC12449769S10OD030463S10 OD030463S10OD026880S10 OD026880K08CA263187P30 AR079200UL1 TR004419T32 AR082315T32AR082315P30AR079200UL1TR004419K08 CA263187Cho IImanishi IKrueger JGGill RKim BSWilder AGuttman-Yassky ERestrepo PNair AJi ALfalseA basophil-fibroblast pro-inflammatory axis fuels type 2 skin inflammation.Chronic inflammatory skin diseases arise from dysregulated interactions between tissue-resident and infiltrating cells, the complexity of which hinders disease understanding and treatment. To address this, here, we present a single-cell spatiotemporal atlas of murine type 2 skin inflammation using MERFISH and scRNA-seq. Analyzing ∼430,000 cells during MC903- and oxazolone-induced dermatitis, we identify 39 cell types, including pro-inflammatory fibroblasts that resemble those in human atopic dermatitis. Spatial neighborhood analyses reveal basophils as potent activators of pro-inflammatory fibroblasts, with basophil-derived oncostatin-M (OSM) and IL-4 synergizing fibroblast-mediated feedforward basophil and immune recruitment. While fibroblast-specific deletion of the IL-4Rα receptor disru2025-01-01T00:00:00Z2025 Aug2026-06-04T07:30:22.21Z2026-06-04T03:06:05.351ZS-EPMC124497694078234910.1016/j.celrep.2025.116114