A cellular census of healthy lung and asthmatic airway wall identifies novel cell states in health and disease

Human lungsenable efficient gas exchange, and form an interface with the environment which depends on mucosal immunity for protection against infectious agents. Tightly controlled interactions between structural and immune cells are required to maintain lung homeostasis. Here, we use single cell transcriptomics to chart the cellular landscape of upper and lower airways and lung parenchyma in health. We report location-dependent airway epithelial cell states, and a novel subset of tissue-resident memory T cells. In lower airways of asthma patients, mucous cellhyperplasia is shown to stem from a novel mucous ciliated cell state, as well as goblet cellhyperplasia. We report presence of pathogenic effector Th2 cells in asthma, and find evidence for type-2 cytokines in maintaining the altered epithelial cell states. Unbiased analysis of cell-cell interactionsidentify a shift from airway structural cell communication in health to a Th2-dominated interactomein asthma.