Antigen presentation by lung epithelial cells directs CD4 + T RM cell function and regulates barrier immunity

Nat Commun. 2021 Oct 5;12(1):5834. doi: 10.1038/s41467-021-26045-w.


Barrier tissues are populated by functionally plastic CD4+ resident memory T (TRM) cells. Whether the barrier epithelium regulates CD4+ TRM cell locations, plasticity and activities remains unclear. Here we report that lung epithelial cells, including distinct surfactant protein C (SPC)lowMHChigh epithelial cells, function as anatomically-segregated and temporally-dynamic antigen presenting cells. In vivo ablation of lung epithelial MHC-II results in altered localization of CD4+ TRM cells. Recurrent encounters with cognate antigen in the absence of epithelial MHC-II leads CD4+ TRM cells to co-express several classically antagonistic lineage-defining transcription factors, changes their cytokine profiles, and results in dysregulated barrier immunity. In addition, lung epithelial MHC-II is needed for surface expression of PD-L1, which engages its ligand PD-1 to constrain lung CD4+ TRM cell phenotypes. Thus, we establish epithelial antigen presentation as a critical regulator of CD4+ TRM cell function and identify epithelial-CD4+ TRM cell immune interactions as core elements of barrier immunity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation / physiology*
  • CD4-Positive T-Lymphocytes / metabolism
  • Epithelial Cells / metabolism*
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Leukocytes / cytology
  • Leukocytes / metabolism
  • Lung / cytology*
  • Lung / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Electron, Transmission
  • Real-Time Polymerase Chain Reaction