TY - JOUR
T1 - A cellular census of human lungs identifies novel cell states in health and in asthma
AU - Vieira Braga, Felipe A.
AU - Kar, Gozde
AU - Berg, Marijn
AU - Carpaij, Orestes A.
AU - Polanski, Krzysztof
AU - Simon, Lukas M.
AU - Brouwer, Sharon
AU - Gomes, Tomás
AU - Hesse, Laura
AU - Jiang, Jian
AU - Fasouli, Eirini S.
AU - Efremova, Mirjana
AU - Vento-Tormo, Roser
AU - Talavera-López, Carlos
AU - Jonker, Marnix R.
AU - Affleck, Karen
AU - Palit, Subarna
AU - Strzelecka, Paulina M.
AU - Firth, Helen V.
AU - Mahbubani, Krishnaa T.
AU - Cvejic, Ana
AU - Meyer, Kerstin B.
AU - Saeb-Parsy, Kourosh
AU - Luinge, Marjan
AU - Brandsma, Corry Anke
AU - Timens, Wim
AU - Angelidis, Ilias
AU - Strunz, Maximilian
AU - Koppelman, Gerard H.
AU - van Oosterhout, Antoon J.
AU - Schiller, Herbert B.
AU - Theis, Fabian J.
AU - van den Berge, Maarten
AU - Nawijn, Martijn C.
AU - Teichmann, Sarah A.
N1 - Publisher Copyright:
© 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2019/7/1
Y1 - 2019/7/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85067892275&partnerID=8YFLogxK
U2 - 10.1038/s41591-019-0468-5
DO - 10.1038/s41591-019-0468-5
M3 - Article
C2 - 31209336
AN - SCOPUS:85067892275
SN - 1078-8956
VL - 25
SP - 1153
EP - 1163
JO - Nature Medicine
JF - Nature Medicine
IS - 7
ER -
