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

Felipe A. Vieira Braga, Gozde Kar, Marijn Berg, Orestes A. Carpaij, Krzysztof Polanski, Lukas M. Simon, Sharon Brouwer, Tomas Gomes, Laura Hesse, Jian Jiang, Eirini S. Fasouli, Mirjana Efremova, Roser Vento-Tormo, Carlos Talavera-Lopez, Marnix R. Jonker, Karen Affleck, Subarna Palit, Paulina M. Strzelecka, Helen V. Firth, Krishnaa T. MahbubaniAna Cvejic, Kerstin B. Meyer, Kourosh Saeb-Parsy, Marjan Luinge, Corry-Anke Brandsma, Wim Timens, Ilias Angelidis, Maximilian Strunz, Gerard H. Koppelman, Antoon J. van Oosterhout, Herbert B. Schiller, Fabian J. Theis, Maarten van den Berge, Martijn C. Nawijn*, Sarah A. Teichmann

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

131 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1153-1163
Number of pages24
JournalNature Medicine
Volume25
Issue number7
Early online date17-Jun-2019
DOIs
Publication statusPublished - Jul-2019

Keywords

  • EPITHELIAL-CELLS
  • PROSTAGLANDIN D-2
  • RNA-SEQ
  • EXPRESSION
  • INFLAMMATION
  • PATHOGENESIS
  • MACROPHAGES
  • PHENOTYPE
  • DISEASE
  • GENE

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