Fig. 6: Interplay between SLC27A2⁺ EpCs and Th2/ILC2 cells through the IL-13 signaling pathway in ECRSwNP.

a A heat map depicting cell–cell interaction strengths between immune cell types with SLC27A2⁻ and SLC27A2⁺ EpC. b Heat maps illustrating the interaction profiles between immune cell types with SLC27A2⁻ and SLC27A2⁺ EpC and in eosinophilic (left) and non-eosinophilic CRSwNP (right). The color intensity represents interaction strength (scale 0–1.5), with darker red indicating stronger interactions. c Chord diagrams illustrating the predicted IL-4/IL-13 signaling from EpC and T and NK cell types in ECRSwNP (left). Circular plots depicting the contribution of each cell type to the overall IL-13 signaling in ECRSwNP (right). The thickness of the lines corresponds to the signal intensity, with thicker lines indicating stronger signaling. d UMAP plots (left) depicting SLC27A2⁻ and SLC27A2⁺ EpC in NPs. IL4R and IL13RA1 expression is color indicated. A violin plot (right) showing the expression levels of IL4R and IL13RA1 in SLC27A2⁻ and SLC27A2⁺ EpC. e A volcano plot demonstrating the transcriptomic expression differences between resting hNECs and IL-4/IL-13 co-stimulated hNECs (GSE268072, resting hNECs n = 5 and IL-4/IL-13 co-stimulated hNECs n = 5). Genes with a significant false discovery rate <0.05 and a >2-fold difference in expression level with an average FPKM >2 are represented by colored dots (red, upregulated gene in IL-4/IL-13 co-stimulated hNECs; blue, downregulated gene in IL-4/IL-13 co-stimulated hNECs). f FPKM values of IL4R and IL13RA1 in ALI-cultured hNECs under resting conditions and IL-4/IL-13 co-stimulation (n = 5 per group). g mRNA expression levels of IL4R and IL13RA1, quantified via RT–qPCR and normalized to GAPDH mRNA, in ALI-cultured hNEC in healthy individuals (n = 8) and patients with CRSwNP (n = 7). h Single-cell transcriptomic profiles of nasal cells from patients with CRSwNP before and after dupilumab treatment (dupilumab data from ref. ¹⁰; pretreatment n = 2 and post-treatment n = 3 patients). UMAP of 11,203 single-cell transcriptomes colored by cell type annotations (left) and dupilumab treatment status (right). i GO analysis of the 241 downregulated genes by dupilumab in EpC clusters, performed using Metascape. j A dot plot showing the expression changes of genes associated with lipid peroxidation before and after treatment with dupilumab. P values were derived from a Wilcoxon signed-rank test (d). * P < 0.05, **P < 0.01, ***P < 0.001 and ****P < 0.0001.