Fig 2: Basophil depletion in vivo leads to a reduction in pro-inflammatory fibroblasts(A) Experimental outline of IgG control vs. anti-FcεRI (MAR-1) in MC903 dermatitis. i.p., intraperitoneal.(B) Basophil quantification in IgG control vs. MAR-1 at d6 MC903. Data are mean ± S.E.M. ***p < 0.001, Mann-Whitney test. Scale bars, 50μm.(C) Representative clinical gross images and H&E staining from d6 MC903.(D) Skin thickness quantification of IgG control vs. MAR-1-treated animals at d6 MC903. Data are mean ± S.E.M. ****p < 0.0001, two-ANOVA.(E) CD45+ proportion in IgG control vs. MAR-1-treated mice at d6 MC903. Data are mean ± S.E.M. ****p < 0.0001, Mann-Whitney test.(F) Principal component analysis (PCA) of bulk RNA-seq of tissues. Each point is an individual animal.(G) Gene Ontology (GO) terms enriched in downregulated genes in MAR-1 vs. IgG control-treated animals.(H) Volcano plot of differentially expressed genes in MAR-1 vs. IgG control-treated animals.(I) Representative IF staining of pSTAT3 (red) and PDGFRA (green) in IgG control vs. MAR-1-treated tissues at d6 MC903, with quantification at right. Low-magnification scale bars, 50 μm; high-magnification scale bars, 10 μm. **p = 0.0022, Mann-Whitney test. In (I–K), the dotted white line marks the epidermis and hair follicle boundary from the dermis.(J) Same as (I), but for IL4RA (green) and PDGFRA (red). Scale bars, 50 μm. *p = 0.024, Mann-Whitney test.(K) Same as (I) and (J), but for TNC (red) staining. Scale bars, 50 μm. **p = 0.0023, Mann-Whitney test.(L) qPCR in IgG control vs. MAR-1-treated animals at d6 MC903. Data are mean ± S.E.M. *p < 0.05, Mann-Whitney test.See also Figure S5 and Table S4.

Fig 3: Inhibition of gp130, or IL6ST, with fibroblast-specific Il4ra deletion leads to significant improvement in inflammation(A) Experimental outline of Il4rafl/fl vs. Il4raΔPdgfra mice treated with vehicle or SC144 during MC903.(B) Representative IF staining of pSTAT3 (red) and PDGFRA (green) in Il4rafl/fl and Il4raΔPdgfra with vehicle or SC144 in d7 MC903, quantified at right. *p < 0.05, **p < 0.01, one-way ANOVA with Dunn’s multiple comparisons test.(C) Representative gross clinical images and H&E from Il4rafl/fl vs. Il4raΔPdgfra mice with vehicle or SC144 at d7 MC903.(D) Skin thickness measurements of Il4rafl/fl vs. Il4raΔPdgfra mice with vehicle or SC144 at d7 MC903. Data are mean ± S.E.M. *p < 0.05, ***p < 0.001, one-way ANOVA with Tukey’s multiple comparisons test.(E) Skin thickness quantification of Il4rafl/fl vs. Il4raΔPdgfra mice with vehicle or SC144 at d7 MC903. Data are mean ± S.E.M. *p < 0.05, ***p < 0.001, one-way ANOVA with Tukey’s multiple comparisons test.(F) CD45+ proportion in Il4rafl/fl vs. Il4raΔPdgfra mice at d7 MC903. Data are mean ± S.E.M. *p < 0.05, **p < 0.01, one-way ANOVA with Tukey’s multiple comparisons test.(G) Proposed model of basophil-induced OSM and IL-4/13 synergistic stimulation of pro-inflammatory fibroblasts that recruit immune cells to promote inflammation.