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Series GSE230512 Query DataSets for GSE230512
Status Public on Feb 15, 2024
Title IL-17 activates dermal reticular fibroblasts to promote neutrophil recruitment and host defense [scRNAseq]
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary The complex system by which the skin regulates immune responses to the external environment is unclear. Here, we investigated cell-cell interactions underlying cutaneous defense against S. aureus. Single-cell transcriptomics (scRNA-Seq) and unbiased network analysis revealed unexpected, dominant IL-17-mediated dermal reticular fibroblast-to-neutrophil communication. Multi-faceted in vitro omics studies demonstrated that IL-17 synergized with several factors including TNF⍺ to induce fibroblast NFKBIZ and chemokine secretion. Cultured fibroblasts drove robust neutrophil recruitment through NFKBIZ-dependent CXCR2 and CXCR4 ligands. Mice lacking IL-17R in fibroblasts (PdgfraΔIl17ra) were generated to determine the significance of fibroblast-neutrophil communication. PdgfraΔIl17ra mice exhibited drastically reduced skin neutrophilia in multiple disease models and reduced defense against S. aureus. These findings were translated to humans by comprehensive analysis of biopsies from psoriasis patients on and off anti-IL-17 treatment. Thus, dermal fibroblasts are critical for skin type 17 inflammation and represent a novel target for treatment of infection and inflammatory disease.
Overall design scRNA-seq of fibroblasts stimulated in vitro and infected, inflamed, and control mouse skin
Contributor(s) Cavagnero KJ
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Submission date Apr 25, 2023
Last update date Feb 16, 2024
Contact name Kellen Cavagnero
Organization name Univeristy of California, San Diego
Street address 9500 Gilman Dr
City San Diego
State/province California
ZIP/Postal code 92093
Country USA
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (6)
GSM7225686 Skin, Intradermal S. aureus infection, control
GSM7225687 Skin, Intradermal S. aureus infection, infected
GSM7225688 Skin, Topical imiquimod, control
This SubSeries is part of SuperSeries:
GSE230513 IL-17 activates dermal reticular fibroblasts to promote neutrophil recruitment and host defense
BioProject PRJNA961680

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Supplementary file Size Download File type/resource
GSE230512_RAW.tar 660.6 Mb (http)(custom) TAR (of MTX, TSV)
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Raw data are available in SRA
Processed data provided as supplementary file

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