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

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.

Automated summary

Single-cell transcriptomics provides detailed information on cell types in the human lung, but lacks spatial context. In this study, we used multi-omic single cell/nuclei and spatial transcriptomics to explore the tissue architecture of healthy human lungs. Through computational analysis, we identified previously unannotated cell types and discovered tissue compartments in different micro-environments. We also uncovered a survival niche for IgA plasma cells in the submucosal glands of the airways, which has implications for respiratory health.