Plate IV.349 · Publications

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

Article in Nature Medicine, 17 June 2019.

Research area: Lung, Epithelial Cells

Authors

  1. Felipe A. Vieira Braga
  2. Gozde Kar
  3. Marijn Berg
  4. Orestes A. Carpaij
  5. Krzysztof Polanski
  6. Lukas M. Simon
  7. Sharon Brouwer
  8. Tomás Gomes
  9. Laura Hesse
  10. Jian Jiang
  11. Eirini S. Fasouli
  12. Mirjana Efremova
  13. Roser Vento-Tormo
  14. Carlos Talavera-López
  15. Marnix R. Jonker
  16. Karen Affleck
  17. Subarna Palit
  18. Paulina M. Strzelecka
  19. Helen V. Firth
  20. Krishnaa T. Mahbubani
  21. Ana Cvejic
  22. Kerstin B. Meyer
  23. Kourosh Saeb-Parsy
  24. Marjan Luinge
  25. Corry-Anke Brandsma
  26. Wim Timens
  27. Ilias Angelidis
  28. Maximilian Strunz
  29. Gerard H. Koppelman
  30. Antoon J. van Oosterhout
  31. Herbert B. Schiller
  32. Fabian J. Theis
  33. Maarten van den Berge
  34. Martijn C. Nawijn
  35. Sarah A. Teichmann

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.

Cite

@article{vieirabraga2019cellular_ffb5,
  title = {{A cellular census of human lungs identifies novel cell states in health and in asthma}},
  author = {Vieira Braga, Felipe A. and Kar, Gozde and Berg, Marijn and Carpaij, Orestes A. and Polanski, Krzysztof and Simon, Lukas M. and Brouwer, Sharon and Gomes, Tomás and Hesse, Laura and Jiang, Jian and Fasouli, Eirini S. and Efremova, Mirjana and Vento-Tormo, Roser and Talavera-López, Carlos and Jonker, Marnix R. and Affleck, Karen and Palit, Subarna and Strzelecka, Paulina M. and Firth, Helen V. and Mahbubani, Krishnaa T. and Cvejic, Ana and Meyer, Kerstin B. and Saeb-Parsy, Kourosh and Luinge, Marjan and Brandsma, Corry-Anke and Timens, Wim and Angelidis, Ilias and Strunz, Maximilian and Koppelman, Gerard H. and van Oosterhout, Antoon J. and Schiller, Herbert B. and Theis, Fabian J. and van den Berge, Maarten and Nawijn, Martijn C. and Teichmann, Sarah A.},
  journal = {Nature Medicine},
  publisher = {Springer Science and Business Media LLC},
  year = {2019},
  month = jun,
  doi = {10.1038/s41591-019-0468-5},
  url = {https://doi.org/10.1038/s41591-019-0468-5},
  pmid = {31209336}
}
.bib file