1. A cellular census of healthy lung and asthmatic airway wall identifies novel cell states in health and disease
- Author
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Marijn Berg, Martijn C. Nawijn, Fabian J. Theis, Paulina M. Strzelecka, Marjan Luinge, Maximilian Strunz, Corry-Anke Brandsma, Subarna Palit, Kerstin B. Meyer, Herbert B. Schiller, Eirini S. Fasouli, Gozde Kar, Ana Cvejic, Antonius van Oosterhout, Orestes A Carpaij, J Jiang, Felipe A. Vieira Braga, krystof polanski, Maarten van den Berge, Kourosh Saeb-Parsy, Tomás Gomes, Sarah A. Teichmann, Lucas Simon, Mirjana Efremova, Roser Vento-Tormo, Karen Affleck, Laura Hesse, Helen V. Firth, W. Timens, Sharon Brouwer, Ilias Angelidis, Gerard H. Koppelman, Krishnaa T. Mahbubani, Groningen Research Institute for Asthma and COPD (GRIAC), and Guided Treatment in Optimal Selected Cancer Patients (GUTS)
- Subjects
0303 health sciences ,Cell signaling ,Lung ,business.industry ,Effector ,Cell ,Hyperplasia ,respiratory system ,medicine.disease ,3. Good health ,respiratory tract diseases ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,Immune system ,030228 respiratory system ,Immunology ,Parenchyma ,medicine ,Airway ,business ,030304 developmental biology - Abstract
SummaryHuman 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.