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

Braga FAV, Kar G, Berg M, Carpaij OA, Polanski K, Simon LM, Brouwer S, Gomes T, Hesse L, Jiang J, Fasouli ES, Efremova M, Vento-Tormo R, Talavera-Lopez C, Jonker MR, Affleck K, Palit S, Strzelecka PM, Firth HV, Mahbubani KT, Cvejic A, Meyer KB, Saeb-Parsy K, Luinge M, Brandsma CA, Timens W, Angelidis I, Strunz M, Koppelman GH, Van Oosterhout AJ, Schiller HB, Theis FJ, Van Den Berge M, Nawijn MC, Teichmann SA (2019)

Publication Type: Journal article

Publication year: 2019

Journal

Nature Medicine Nature Publishing Group

Book Volume: 25

Pages Range: 1153-1163

Journal Issue: 7

DOI: 10.1038/s41591-019-0468-5

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 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 cell hyperplasia is shown to stem from a novel mucous ciliated cell state, as well as goblet cell hyperplasia. We report the presence of pathogenic effector type 2 helper T cells (TH2) in asthmatic lungs and find evidence for type 2 cytokines in maintaining the altered epithelial cell states. Unbiased analysis of cell–cell interactions identifies a shift from airway structural cell communication in healthy lungs to a TH2-dominated interactome in asthmatic lungs.

Involved external institutions

University of Groningen / Rijksuniversiteit Groningen NL Netherlands (NL) Deutsches Zentrum für Lungenforschung e.V. (DZL) DE Germany (DE) Wellcome Trust Sanger Institute - Genome Research Limited GB United Kingdom (GB) Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich DE Germany (DE) GlaxoSmithKline plc. (GSK) GB United Kingdom (GB) University of Cambridge GB United Kingdom (GB)

How to cite

APA:

Braga, F.A.V., Kar, G., Berg, M., Carpaij, O.A., Polanski, K., Simon, L.M.,... Teichmann, S.A. (2019). A cellular census of human lungs identifies novel cell states in health and in asthma. Nature Medicine, 25(7), 1153-1163. https://doi.org/10.1038/s41591-019-0468-5

MLA:

Braga, Felipe A. Vieira, et al. "A cellular census of human lungs identifies novel cell states in health and in asthma." Nature Medicine 25.7 (2019): 1153-1163.

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