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Nat Med. 2019 Jul;25(7):1153-1163. doi: 10.1038/s41591-019-0468-5. Epub 2019 Jun 17.

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

Author information

1
Wellcome Sanger Institute, Cambridge, UK.
2
Open Targets, Cambridge, UK.
3
Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
4
Groningen Research Institute for Asthma and COPD, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
5
Department of Pulmonology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
6
Institute of Computational Biology, Helmholtz Zentrum München, Neuherberg, Germany.
7
Allergic Inflammation Discovery Performance Unit, Respiratory Therapy Area, GlaxoSmithKline, Stevenage, UK.
8
TranslaTUM, Technische Universität München, Munich, Germany.
9
Institute of Virology, Technische Universität München, Munich, Germany.
10
German Center for Infection Research, Partner Site Munich, Munich, Germany.
11
Department of Haematology, University of Cambridge, Cambridge, UK.
12
Cambridge Stem Cell Institute, Cambridge, UK.
13
Department of Surgery, NIHR Cambridge Biomedical Research Centre, University of Cambridge, Cambridge, UK.
14
Helmholtz Zentrum München, Institute of Lung Biology and Disease, Member of the German Center for Lung Research (DZL), Munich, Germany.
15
Department of Pediatric Pulmonology and Pediatric Allergology, Beatrix Children's Hospital, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
16
Department of Mathematics, Technische Universität München, Garching, Germany.
17
Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands. m.c.nawijn@umcg.nl.
18
Groningen Research Institute for Asthma and COPD, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands. m.c.nawijn@umcg.nl.
19
Wellcome Sanger Institute, Cambridge, UK. st9@sanger.ac.uk.
20
Open Targets, Cambridge, UK. st9@sanger.ac.uk.
21
Theory of Condensed Matter Group, Cavendish Laboratory, Department of Physics, University of Cambridge, Cambridge, UK. st9@sanger.ac.uk.

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.

PMID:
31209336
DOI:
10.1038/s41591-019-0468-5

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