A basophil-fibroblast pro-inflammatory axis fuels type 2 skin inflammation
- Cell Rep. 2025 Aug 26;44(8):116114. doi: 10.1016/j.celrep.2025.116114.
- 1. Kimberly and Eric J. Waldman Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Black Family Stem Cell Institute, Institute for Regenerative Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
- 2. Kimberly and Eric J. Waldman Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Black Family Stem Cell Institute, Institute for Regenerative Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
- 3. Laboratory for Investigative Dermatology, Rockefeller University, New York, NY 10065, USA.
- 4. Kimberly and Eric J. Waldman Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
- 5. Kimberly and Eric J. Waldman Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Mark Lebwohl Center for Neuroinflammation and Sensation, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Allen Discovery Center for Neuroimmune Interactions, New York, NY 10029, USA; Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
- 6. Kimberly and Eric J. Waldman Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Black Family Stem Cell Institute, Institute for Regenerative Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address: [email protected].
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.