AI Article Synopsis
- * Using single-cell RNA sequencing, researchers found that IL-13 triggers significant changes in these cells, turning them into mucus-producing cells while causing damage to ciliated cells.
- * The changes in the airway epithelium due to IL-13 lead to unhealthy mucus production and hinder normal airway function, highlighting potential targets for asthma treatment.
Article Abstract
The type 2 cytokine-high asthma endotype (T2H) is characterized by IL-13-driven mucus obstruction of the airways. To further investigate this incompletely understood pathobiology, we characterize IL-13 effects on human airway epithelial cell cultures using single-cell RNA sequencing, finding that IL-13 generates a distinctive transcriptional state for each cell type. Specifically, we discover a mucus secretory program induced by IL-13 in all cell types which converts both mucus and defense secretory cells into a metaplastic state with emergent mucin production and secretion, while leading to ER stress and cell death in ciliated cells. The IL-13-remodeled epithelium secretes a pathologic, mucin-imbalanced, and innate immunity-depleted proteome that arrests mucociliary motion. Signatures of IL-13-induced cellular remodeling are mirrored by transcriptional signatures characteristic of the nasal airway epithelium within T2H versus T2-low asthmatic children. Our results reveal the epithelium-wide scope of T2H asthma and present candidate therapeutic targets for restoring normal epithelial function.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046336 | PMC |
| http://dx.doi.org/10.1016/j.celrep.2020.107872 | DOI Listing |
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