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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
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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.
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Overall design |
scRNA-seq of fibroblasts stimulated in vitro and infected, inflamed, and control mouse skin
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Contributor(s) |
Cavagnero KJ |
Citation missing |
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Submission date |
Apr 25, 2023 |
Last update date |
Feb 16, 2024 |
Contact name |
Kellen Cavagnero |
E-mail(s) |
kecavagn@health.ucsd.edu
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Organization name |
Univeristy of California, San Diego
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Street address |
9500 Gilman Dr
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City |
San Diego |
State/province |
California |
ZIP/Postal code |
92093 |
Country |
USA |
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Platforms (1) |
GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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Samples (6)
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GSM7225686 |
Skin, Intradermal S. aureus infection, control |
GSM7225687 |
Skin, Intradermal S. aureus infection, infected |
GSM7225688 |
Skin, Topical imiquimod, control |
GSM7225689 |
Skin, Topical imiquimod, imq |
GSM7225690 |
Fibroblast in vitro IL-17A + TNFa, control |
GSM7225691 |
Fibroblast in vitro IL-17A + TNFa, stimulated |
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This SubSeries is part of SuperSeries: |
GSE230513 |
IL-17 activates dermal reticular fibroblasts to promote neutrophil recruitment and host defense |
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Relations |
BioProject |
PRJNA961680 |