FA Vieira Braga, G Kar, M Berg, OA Carpaij, K Polanski, LM Simon, S Brouwer, T Gomes, L Hesse, J Jiang, ES Fasouli, M Efremova, R Vento-Tormo, C Talavera-López, MR Jonker, K Affleck, S Palit, PM Strzelecka, HV Firth, KT Mahbubani, A Cvejic, KB Meyer, K Saeb-Parsy, M Luinge, C-A Brandsma, W Timens, I Angelidis, M Strunz, GH Koppelman, AJ van Oosterhout, HB Schiller, FJ Theis, M van den Berge, MC Nawijn, SA Teichmann
Journal name: 
Nat Med
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.
E-pub date: 
31 May 2019
Users with this publication listed: 
Kerstin Meyer