Journal: Nature Communications

Article Title: Airway immune profiles and therapeutic implications of IGF1 in eosinophilic granulomatosis with polyangiitis

doi: 10.1038/s41467-025-68104-6

Figure Lengend Snippet: a Immunofluorescent staining and quantification of IGF1⁺ epithelial cells at bronchial mucosae from control ( n = 6), SEA ( n = 9), EGPA ( n = 10), Cs-remission ( n = 3), and Cs-relapse ( n = 5) groups (biological replicates). Scale bar: 100 μm. b Bar plots of IGF1 concentrations in sputum samples from Control ( n = 13), SEA ( n = 23), and EGPA ( n = 21) (biological replicates). c Schematic of EGPA airway epithelial cells in ALI culture stimulated with IL-13, IL-33, or medium (Control). Bar plots show relative expression of IGF1 , IGF1R , and IGFBP3 , and IGF1 concentrations under different conditions. Data from 3 independent experiments (biological replicates). d Schematic of ALI system with IGF1 stimulation versus control. Representative histological (HE, PAS) and immunofluorescent (MUC5AC with DAPI) staining demonstrate morphological changes and mucin production (goblet hyperplasia) in ALI cultures with medium (Control) or IGF1 stimulation. Scale bars: 50 μm (HE, PAS), 20 μm (MUC5AC). Bar plots of IL-25, IL-33, and TSLP concentrations in culture supernatant at time points (Day 9, 13, 17, 21). Data from 3 independent experiments (biological replicates). e Scatter plot showing positive correlation between eosinophil abundance and IGF1 concentration in sputum from EGPA patients ( n = 21). f Schematic of proposed mechanism where IGF1 promotes goblet hyperplasia and augments T2-mediated inflammation through IGF1-IL25 loop, contributing to disease exacerbation in asthma and EGPA. Data presented as mean ± SD. a – c Two-sided one-way ANOVA with Tukey’s post-hoc test. d Two-sided unpaired t -test. e Two-sided Pearson correlation test. * P < 0.05, ** P < 0.01, *** P < 0.001; NS, not significant. Exact P values in Supplementary Data . ALI air-liquid interface, HE hematoxylin and eosin, IGF1R insulin-like growth factor 1 receptor, IGFBP3 insulin-like growth factor binding protein 3, PAS periodic acid-Schiff, TSLP thymic stromal lymphopoietin.

Article Snippet: Mice were administered 50 μg of low-endotoxin HDM (Greer Labs, Cat# XPB91D3A2.5) combined with 500 ng recombinant mouse IL-33 (PEPROTECH, Cat# 210-33) via intranasal injection (i.n.) at Day 0, Day 7, Day 14 and Day 21, and recombinant IL−25 (2 μg in 50 μL saline, recombinant mouse IL25, R&D System, Cat# 1399-IL-025) was administered via intranasal injection (i.n.) at Day 15, Day 17, Day 19, and Day 21, Mice were sacrificed at Day 24, and tissues were harvested for downstream analysis.

Techniques: Staining, Control, Expressing, Concentration Assay, Binding Assay

Journal: Nature Communications

Article Title: Airway immune profiles and therapeutic implications of IGF1 in eosinophilic granulomatosis with polyangiitis

doi: 10.1038/s41467-025-68104-6

Figure Lengend Snippet: a – e Anti-IGF1 treatment reduces eosinophilic inflammation and airway remodeling in IL-5 transgenic mice challenged with HDM and IL-33. Mice were divided into Control (PBS-treated), Model (HDM+IL-33 challenged), and Anti-IGF1 (HDM+IL-33+anti-IGF1 antibody) groups. a Total cell counts in bronchoalveolar lavage fluid (BALF) from control, model, and anti-IGF1-treated groups. b Eosinophil percentage in BALF. c Absolute eosinophil counts in BALF. d IL−25 levels in BALF quantified by ELISA. e Representative histological images of lung sections stained with hematoxylin and eosin (H&E, upper panels) and periodic acid-Schiff (PAS, lower panels), with corresponding inflammation and PAS score quantifications. Scale bar, 100 μm. f – h IGF1R deficiency modulates eosinophilic inflammation and airway remodeling via IL−25 in HDM+IL-33 challenged mice. f Total cell counts in BALF from wild-type (WT, Scgb1a1 -IRES-+/+ Igf1r f/f ), conditional knockout ( Scgb1a1 -IRES-Cre/+ Igf1r f/f , CKO), and CKO mice treated with recombinant IL-25 (rIL-25). All groups were challenged with HDM+IL-33. g Flow cytometric analysis of eosinophils (CD45 + Siglec-F + CD11c - ) in BALF. Representative plots and quantification of eosinophil percentages are shown. h Representative H&E (upper panels) and PAS (lower panels) staining of lung sections from WT, CKO, and CKO+rIL-25 groups, with quantification of inflammation and PAS scores. Scale bar, 100 μm. Statistical analysis: Data are presented as mean ± SD ( n = 5 mice per group). Statistical significance was determined using a two-sided one-way ANOVA with Tukey’s post hoc test. * p < 0.05; ** p < 0.01; *** p < 0.001; NS, not significant. Exact P values and complete test statistics for a – h are provided in Supplementary Data . CKO conditional knockout, HDM house dust mite, rIL-25 recombinant IL-25, WT wild-type.

Article Snippet: Mice were administered 50 μg of low-endotoxin HDM (Greer Labs, Cat# XPB91D3A2.5) combined with 500 ng recombinant mouse IL-33 (PEPROTECH, Cat# 210-33) via intranasal injection (i.n.) at Day 0, Day 7, Day 14 and Day 21, and recombinant IL−25 (2 μg in 50 μL saline, recombinant mouse IL25, R&D System, Cat# 1399-IL-025) was administered via intranasal injection (i.n.) at Day 15, Day 17, Day 19, and Day 21, Mice were sacrificed at Day 24, and tissues were harvested for downstream analysis.

Techniques: Transgenic Assay, Control, Enzyme-linked Immunosorbent Assay, Staining, Knock-Out, Recombinant