Single-Cell and Population Transcriptomics Reveal Pan-epithelial Remodeling in Type 2-High Asthma

• DOI: 10.1016/j.celrep.2020.107872
• Publication Date: 2020-07-07T14:52:55Z
• Authors: Nathan D. Jackson; Jamie L. Everman; Maurizio Chioccioli; Luigi Feriani; Katherine C. Gold...; Satria P. Sajuthi; Cydney L. Rios; Roger Powell; Michael Armstrong; Joe Gomez; Cole Michel; Celeste Eng; Sam S. Oh; Jose Rodriguez-Sa...; Pietro Cicuta; Nichole Reisdorph; Esteban G. Burchard; Max A. Seibold
• Keywords: Cell type

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 generates a distinctive transcriptional state for each type. Specifically, discover secretory program induced in all types which converts both and defense cells into metaplastic with emergent mucin production secretion, while leading to ER stress death ciliated cells. IL-13-remodeled epithelium secretes pathologic, mucin-imbalanced, innate immunity-depleted proteome arrests mucociliary motion. Signatures IL-13-induced cellular remodeling are mirrored signatures characteristic nasal within T2H versus T2-low asthmatic children. Our results reveal epithelium-wide scope present candidate therapeutic targets restoring normal function.