Fig. 6: Functional implication of 15LO1-dependent ferroptosis.

A Fewer ciliated cells under IL-13 compared to control conditions by SEM (upper panel) and TEM (lower panel) (n = 3 biological replicates). Green arrows: cilia; Red arrows: areas denuded of cilia. Blue arrows: “healthy” mitochondria; Yellow arrows: decreased mitochondria. B Loss of cilia and mitochondria, as well as presence of swollen mitochondria in fresh epithelial cells from a severe asthmatic compared to HC participant (TEM) (n = 3–5 samples from individual donors in each group). Green arrows: cilia; Red arrows: areas denuded of cilia. Blue arrows: “healthy” mitochondria; Yellow arrows: swollen mitochondria. C FER-1 (1 µM, 5 days) and/or BLX2477(2 µM, 5 days) prevent IL-13-induced cilia structural changes and ciliated cell loss by SEM (upper panel) and by tubulin staining (IF/CF, bottom panel). D Under the same conditions, FER-1 and BLX2477 increase TUB1A expression by WB under IL-13 conditions. Representative images n = 3 biological replicates. E Representative images of fresh epithelial cells with varying cilia length (Diff-Quik staining) (n = 38 individual donors, see Table 3 for Demographics). F Percentages of total mature epithelial cells ex vivo with no/or short cilia negatively correlate with FEV1% predicted and (G) 15LO1 protein (by WB of same cells) positively correlate with percentage of cells with no/short cilia (Bivariate linear correlation). H Mediation analysis supports that the majority of the potential impact of 15LO1 on lung function (FEV1% predicted) is through effects on ciliated cell phenotype. Data quantification and individual antibody images in Supplementary Fig. 6. Source data provided as Source Data file.