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

Felipe Vieira Braga, Gozde Kar, Marijn Berg, Orestes Carpaij, krystof polanski, Lucas Simon, Sharon Brouwer, Tomas Gomes, Laura Hesse, J Jiang, E.S. Fasouli, M Efremova, R Vento-Tormo, Karen Affleck, S Palit, p strzelecka, Helen V. Firth, K.T.A. Mahbubani, Ana Cvejic, K MeyerK Saeb-Parsy, Marjan Luinge, C. Brandsma, Willem Timens, I Angelidis, M Strunz, Gerard Koppelman, Antonius van Oosterhout, H. B. Schiller, F. Theis, Maarten van den Berge, Martijn Nawijn*, Sarah A Teichmann

*Corresponding author for this work

Research output: Contribution to journalArticleAcademic

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Abstract

Human lungs enable 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 cell hyperplasia is shown to stem from a novel mucous ciliated cell state, as well as goblet cell hyperplasia. 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 interactions identify a shift from airway structural cell communication in health to a Th2-dominated interactome in asthma.
Original languageEnglish
JournalbioRxiv
DOIs
Publication statusSubmitted - 23-Jan-2019

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