(A) IL-6 and IL-11 protein secreted by control or IPF primary human lung fibroblast (HLF). Error bars represent SEM. Mann-Whitney test used for statistical comparison. (B) IL-6 and IL-11 gene expression by control or IPF HLF. Error bars represent SEM. Mann-Whitney test used for statistical comparison. (C) Schematic of HLF-airway epithelial coculture. (D) Epithelial speed across days of air-liquid interface (ALI) in monoculture and epithelial-HLF coculture conditions. Error bars represent 95% confidence interval. (E) Histogram of cellular aspect ratio (AR) with mean values from mono- and coculture epithelia at ALI day 14 with comparisons to control or IPF monocultures. One-way ANOVA was used for statistical comparison. (F) Representative images of segmented cultures at day 14 of ALI in mono- or co-culture conditions color coded on the basis of cell AR. Scale bar, 100 μm. (G) KEGG enrichment for genes up-regulated in epithelial cells under co-culture conditions when compared with control epithelial monocultures. (H) Top differentially regulated genes in mono- and coculture conditions selected for genes shared between cocultured and IPF monocultured epithelia. (I) Shared genes from HLF cocultured epithelia and IL-6/sIL-6R stimulated airway epithelial monocultures (GSE 113185). (J) Speed of cocultures at day 14 of ALI treated with IL-6–related inhibitors (anti–IL-6 antibody, anti–IL-6R antibody, and gp130-Fc chimera). Error bars represent SEM. One-way ANOVA used for statistical comparison. (A to J) For all statistical analysis n.s. (not significant), **P < 0.01, ***P < 0.001, ****P < 0.0001. Cell culture experiments were independently performed N ≥ 3 times with n = 4 donors.