A cellular census of human lungs identifies novel cell states in health and in asthma

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 lunghomeostasis. Here, we use single-cell transcriptomics to chart the cellular landscape of upper and lower airways and lungparenchyma in healthy lungs, and lower airways in asthmatic lungs. We report location-dependent airway epithelial cell states and a novel subset of tissue-resident memory T cells. In the lower airways of patients with asthma, mucous cellhyperplasia is shown to stem from a novel mucous ciliated cell state, as well as goblet cellhyperplasia. We report the presence of pathogenic effector type 2 helper T cells (TH2) in asthmatic lungsand find evidence for type 2 cytokines in maintaining the altered epithelial cell states. Unbiased analysis of cell–cell interactionsidentifies a shift from airway structural cell communication in healthy lungsto a TH2-dominated interactomein asthmatic lungs.