Fig. 4: Treatment refractory EGPA exhibit increased IGF1⁺ macrophages, goblet hyperplasia and mucin production. | Nature Communications

Fig. 4: Treatment refractory EGPA exhibit increased IGF1⁺ macrophages, goblet hyperplasia and mucin production.

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

Fig. 4: Treatment refractory EGPA exhibit increased IGF1⁺ macrophages, goblet hyperplasia and mucin production.

a UMAP plots of 12 macrophage and DC subtypes from baseline and follow-up samples. IGF1⁺Macrophage cluster (cluster 3) highlighted. b Volcano plot of DEGs in IGF1⁺ macrophages between baseline and follow-up. Upregulated (red), downregulated (blue), stable (grey) genes shown. c Bar plots of top enriched Reactome pathways in IGF1⁺ macrophages from DEGs (two-sided Wilcoxon rank-sum test, adjusted P values). Pathway enrichment of top 20 upregulated genes via Enrichr (Reactome_Pathways_2024, hypergeometric test, unadjusted P values). d UMAP plots of key marker gene expression (HP, IGF1, RETN) in macrophage subsets; color intensity reflects normalized UMI counts. e Violin plots of IGF1, RETN, HP expression across disease phases (EGPA baseline, Cs-remission, Cs-relapse) in macrophages. f Immunofluorescent staining and quantification of IGF1⁺CD68⁺ macrophages in bronchial mucosae (biological replicates; EGPA n = 15, Cs-remission n = 3, Cs-relapse n = 5). Scale bars: 100 μm (upper), 20 μm (lower). g UMAP plots of 11 epithelial cell subsets from combined samples. h Heatmap of relative enrichment (observed/expected Ro/e) of epithelial subtypes across groups and sample types. i Dot plot of reciprocal epithelial ligand-receptor expression across subsets. Interaction pairs linked by color-coded lines; dot size reflects expression fraction, color intensity shows relative expression. j Violin plots of marker gene expression for goblet cell subsets (Goblet-1, Goblet−2) and ionocytes across groups. k Immunofluorescent staining and quantification of MUC5AC⁺ epithelial cells (biological replicates; EGPA n = 10, Cs-remission n = 3, Cs-relapse n = 5). Scale bar: 100 μm. Data presented as median with IQR. f, k Two-sided Kruskal–Wallis test with Dunn’s post-hoc and Bonferroni correction. *P < 0.05, **P < 0.01, ***P < 0.001; NS, not significant. Exact P values in Supplementary Data 1. Cs-relapse corticosteroid relapse, Cs-remission corticosteroid remission, DC dendritic cell, DEGs differentially expressed genes, IGF1 insulin-like growth factor 1, MUC5AC mucin 5AC, Ro/e ratio of observed to expected.

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