A basophil-fibroblast pro-inflammatory axis fuels type 2 skin inflammation
Summary: 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 inflammatio...
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| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-08-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S221112472500885X |
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| Summary: | Summary: 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 disrupts inflammation in vivo, the addition of pharmacologic gp130 inhibition, a core component of the OSM receptor, results in synergistic reduction of inflammation. Our study establishes a basophil-fibroblast circuitry as a critical regulator of type 2 skin inflammation, redefining basophil biology and positioning fibroblasts as dynamic immune regulators and therapeutic targets in inflammatory skin disease. |
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| ISSN: | 2211-1247 |