Fig. 6: Notch3 signaling in fibroblasts mediates ILC2 conversion to ILC1s, and is associated with an attenuated fibrotic phenotype.

a Flow plot showing fibroblasts (CD45^–CD140a⁺CD90.2⁺) in CS-treated lungs. Flow histogram and bar graph compare Notch3 MFI values in fibroblasts from saline or CS-treated lungs (saline, n = 4 biological replicates; CS 8–10 weeks, n = 8 biological replicates). b Schematic showing tamoxifen (TAM)-induced fibroblast-specific Notch3 depletion. TAM was applied at early fibrogenesis stages (week 3–4 after CS treatment). c Flow plots showing NKp46⁺(ILC1) and ST-2⁺(ILC2) percentages in lungs (n = 5 biological replicates). Bar graphs compare ILC2 and ILC1 percentages in ILCs and ILC1/ILC2 ratios in lungs. d Masson’s staining showing lung section images of whole lung lobes and zoomed in areas evaluating the degree of pulmonary fibrosis at weeks 8–10 and 12–14 or saline-treated counterparts. Scale bar = 600 μm (upper panel), 200 μm (middle panels), and 50 μm (lower panels). Bar graph compares fibrotic area percentages in sections (n = 5 biological replicates). e Western blot showing FN and Col1 levels in lungs. Uncropped blots are in source data. The bar graph compares relative protein levels in mouse lungs (n = 4 biological replicates). f Hydroxyproline (HYP) content in mouse lungs. The bar graph compares HYP content in lungs (n = 4 biological replicates). g Schematic showing TAM-induced fibroblast-specific Notch3 depletion. TAM was applied at fibrosis progression stage (week 8–9 after CS treatment). h Flow plots showing NK1.1⁺(ILC1) and ST-2⁺(ILC2) percentages in CS-treated mouse lungs (n = 5 biological replicates). Bar graphs compare ILC2 and ILC1 percentages in ILCs and ILC1/ILC2 ratios in lungs. i Schematic showing BLM-induced pulmonary fibrosis and TAM-induced fibroblast-specific Notch3 depletion. TAM was applied at the inflammatory stage (week 1–2 after BLM treatment). j Flow plots showing NKp46⁺ (ILC1) and ST-2⁺ (ILC2) percentages in BLM-treated mouse lungs (n = 5 biological replicates). Bar graphs compare ILC2 and ILC1 percentages in pulmonary ILCs and ILC1/ILC2 ratios in lungs. Bar graphs represent the combined results of four biologically independent experiments with similar results. Individual values are plotted in graphs. Littermate mice were used in experiments. Data are shown as the mean ± SEM. P values were calculated using one-way ANOVA followed by Tukey’s tests (c, d, e, f) or two-tailed unpaired Student’s t-tests (a, h, j). P values are indicated in graphs. Source data are provided in a source data file.