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A spatially resolved atlas of the human lung characterizes a gland-associated immune niche.

Published version
Peer-reviewed

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Authors

Madissoon, Elo 
Kleshchevnikov, Vitalii 
Wilbrey-Clark, Anna 
Polanski, Krzysztof  ORCID logo  https://orcid.org/0000-0002-2586-9576

Abstract

Single-cell transcriptomics has allowed unprecedented resolution of cell types/states in the human lung, but their spatial context is less well defined. To (re)define tissue architecture of lung and airways, we profiled five proximal-to-distal locations of healthy human lungs in depth using multi-omic single cell/nuclei and spatial transcriptomics (queryable at lungcellatlas.org ). Using computational data integration and analysis, we extend beyond the suspension cell paradigm and discover macro and micro-anatomical tissue compartments including previously unannotated cell types in the epithelial, vascular, stromal and nerve bundle micro-environments. We identify and implicate peribronchial fibroblasts in lung disease. Importantly, we discover and validate a survival niche for IgA plasma cells in the airway submucosal glands (SMG). We show that gland epithelial cells recruit B cells and IgA plasma cells, and promote longevity and antibody secretion locally through expression of CCL28, APRIL and IL-6. This new 'gland-associated immune niche' has implications for respiratory health.

Description

Keywords

Humans, Respiratory Mucosa, Lung, Epithelial Cells, B-Lymphocytes, Immunoglobulin A

Journal Title

Nat Genet

Conference Name

Journal ISSN

1061-4036
1546-1718

Volume Title

55

Publisher

Springer Science and Business Media LLC
Sponsorship
European Commission Horizon 2020 (H2020) Societal Challenges (874656)