Revisiting airway epithelial remodeling in type 2 immunity: Beyond goblet cell metaplasia

Advances in single-cell RNA sequencing (scRNA-seq) allow the characterization of cellular states across human tissues with unprecedented granularity, creating opportunities to reassess the diversity of cell states found in health and the molecular networks that drive inflammatory disease. Type 2 inflammation is classically characterized by the recruitment and/or hyperplasia of TH2 cells, type 2 innate lymphoid cells (ILC2s), mast cells, and eosinophils, which promote the generation of IgE and the type 2 cytokines IL-4, IL-5, and IL-13. Although decades of research have elucidated pathobiologic roles for these hematopoietic cells in airway disease and linked them to the development of goblet cell metaplasia, we can now define their maturation and activation in human tissue, as well as the cellular neighborhoods in which they function.

Although few in number, recent scRNA-seq studies in mice and human subjects have highlighted the remarkable cellular diversity of the airway, especially among constituent epithelial cells (EpCs), implicating them in novel proinflammatory pathways that support immune function and promote inflammatory disease.