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

Nat Genet. 2023 Jan;55(1):66-77. doi: 10.1038/s41588-022-01243-4. Epub 2022 Dec 21.

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.

MeSH terms

  • B-Lymphocytes
  • Epithelial Cells / metabolism
  • Humans
  • Immunoglobulin A / metabolism
  • Lung*
  • Respiratory Mucosa* / metabolism

Substances

  • Immunoglobulin A