A spatially resolved atlas of the human lung characterizes a gland-associated immune niche
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Published:2022-12-21
Issue:1
Volume:55
Page:66-77
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ISSN:1061-4036
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Container-title:Nature Genetics
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language:en
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Short-container-title:Nat Genet
Author:
Madissoon Elo, Oliver Amanda J.ORCID, Kleshchevnikov Vitalii, Wilbrey-Clark Anna, Polanski KrzysztofORCID, Richoz Nathan, Ribeiro Orsi AnaORCID, Mamanova LiraORCID, Bolt Liam, Elmentaite RasaORCID, Pett J. PatrickORCID, Huang Ni, Xu Chuan, He PengORCID, Dabrowska Monika, Pritchard Sophie, Tuck LizORCID, Prigmore ElenaORCID, Perera Shani, Knights Andrew, Oszlanczi Agnes, Hunter Adam, Vieira Sara F.ORCID, Patel Minal, Lindeboom Rik G. H.ORCID, Campos Lia S., Matsuo Kazuhiko, Nakayama TakashiORCID, Yoshida MasahiroORCID, Worlock Kaylee B.ORCID, Nikolić Marko Z.ORCID, Georgakopoulos NikitasORCID, Mahbubani Krishnaa T.ORCID, Saeb-Parsy KouroshORCID, Bayraktar Omer AliORCID, Clatworthy Menna R., Stegle Oliver, Kumasaka NatsuhikoORCID, Teichmann Sarah A.ORCID, Meyer Kerstin B.ORCID
Abstract
AbstractSingle-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 atlungcellatlas.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.
Publisher
Springer Science and Business Media LLC
Reference115 articles.
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