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Although these are characteristic features of IPF, knowledge of specific interactions between these pathological processes is limited. Here, the interaction of lung epithelial and lung mesenchymal cells was investigated in a coculture model of human primary airway epithelial cells (EC) and lung fibroblasts (FB). Single-cell RNA sequencing revealed that the starting EC population was heterogenous and enriched for cells with a basal cell signature. Furthermore, fractions of the initial EC and FB populations adopted distinct pro-fibrotic cell differentiation states upon cocultivation, resembling specific cell populations that were previously identified in lungs of patients with IPF. Transcriptomic analysis revealed active NF-\u03baB signaling early in the cocultured EC and FB, and the identified NF-\u03baB expression signatures were found in \u201cHAS1 High FB\u201d and \u201cPLIN2+ FB\u201d populations from IPF patient lungs. Pharmacological blockade of NF-\u03baB signaling attenuated specific phenotypic changes of EC and prevented FB-mediated interleukin-6, interleukin-8, and CXC chemokine ligand 6 cytokine secretion, as well as collagen \u03b1-1(I) chain and \u03b1\u2013smooth muscle actin accumulation. 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