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Asthma is a chronic, heterogeneous disease of the airways, often characterised by structural changes known collectively as airway remodelling. In response to environmental insults, including pathogens, allergens and pollutants, the epithelium can initiate remodelling via an inflammatory cascade involving a variety of mediators that have downstream effects on both structural and immune cells. These mediators include the epithelial cytokines thymic stromal lymphopoietin, interleukin (IL)-33 and IL-25, which facilitate airway remodelling through cross-talk between epithelial cells and fibroblasts, and between mast cells and airway smooth muscle cells, as well as through signalling with immune cells such as macrophages. The epithelium can also initiate airway remodelling independently of inflammation in response to the mechanical stress present during bronchoconstriction. Furthermore, genetic and epigenetic alterations to epithelial components are believed to influence remodelling. Here, we review recent advances in our understanding of the roles of the epithelium and epithelial cytokines in driving airway remodelling, facilitated by developments in genetic sequencing and imaging techniques. We also explore how new and existing therapeutics that target the epithelium and epithelial cytokines could modify airway remodelling., Competing Interests: Conflict of interest: G. Varricchi has received grants from AstraZeneca. C.E. Brightling has received grants and consultancy fees from 4D Pharma, AstraZeneca, Chiesi, Genentech, GSK, Mologic, Novartis, Regeneron Pharmaceuticals, Roche and Sanofi. C. Grainge has received grants from AstraZeneca and industry-sponsored grants from Boehringer Ingelheim and Cyclopharma. B.N. Lambrecht has received grants from the European Research Council, Ghent University, Research Foundation Flanders and the Flanders Institute of Biotechnology, and has received consulting fees from Argenx, AstraZeneca, GSK and Sanofi. P. Chanez has received consultancy fees from ALK, Almirall, AstraZeneca, Boehringer Ingelheim, Boston Scientific, Centocor, Chiesi, GSK, Johnson & Johnson, MSD, Novartis, Sanofi, SNCF and Teva Pharmaceuticals, has received industry-sponsored grants from ALK, AstraZeneca, Boehringer Ingelheim, Boston Scientific, Centocor, Chiesi, GSK, Novartis, Roche and Teva Pharmaceuticals, and is the president of the scientific committee for Fondation du Souffle., (Copyright ©The authors 2024.)