02870nas a2200685 4500000000100000000000100001008004100002260001200043653001800055653002100073653001100094653002100105653000900126653002300135100001800158700002100176700002700197700002300224700002300247700001800270700002100288700001800309700001400327700002000341700002000361700001300381700001300394700001200407700002100419700002100440700001300461700001900474700001700493700001900510700002000529700001600549700001900565700001600584700002400600700001800624700002000642700002100662700002100683700002200704700002200726700002700748700002600775700002300801700002300824700002400847700001800871700002300889700002300912700002100935245009500956300001001051490000701061520110201068022001402170 2023 d c2023-0110aB-Lymphocytes10aEpithelial Cells10aHumans10aImmunoglobulin A10aLung10aRespiratory Mucosa1 aElo Madissoon1 aAmanda J. Oliver1 aVitalii Kleshchevnikov1 aAnna Wilbrey-Clark1 aKrzysztof Polanski1 aNathan Richoz1 aAna Ribeiro Orsi1 aLira Mamanova1 aLiam Bolt1 aRasa Elmentaite1 aJ. Patrick Pett1 aNi Huang1 aChuan Xu1 aPeng He1 aMonika Dabrowska1 aSophie Pritchard1 aLiz Tuck1 aElena Prigmore1 aShani Perera1 aAndrew Knights1 aAgnes Oszlanczi1 aAdam Hunter1 aSara F. Vieira1 aMinal Patel1 aRik G. H. Lindeboom1 aLia S. Campos1 aKazuhiko Matsuo1 aTakashi Nakayama1 aMasahiro Yoshida1 aKaylee B. Worlock1 aMarko Z. Nikolić1 aNikitas Georgakopoulos1 aKrishnaa T. Mahbubani1 aKourosh Saeb-Parsy1 aOmer Ali Bayraktar1 aMenna R. Clatworthy1 aOliver Stegle1 aNatsuhiko Kumasaka1 aSarah A. Teichmann1 aKerstin B. Meyer00aA spatially resolved atlas of the human lung characterizes a gland-associated immune niche a66-770 v553 aSingle-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. a1546-1718