[HTML][HTML] Antigen presentation by lung epithelial cells directs CD4+ TRM cell function and regulates barrier immunity

AT Shenoy, C Lyon De Ana, EI Arafa, I Salwig… - Nature …, 2021 - nature.com
AT Shenoy, C Lyon De Ana, EI Arafa, I Salwig, KA Barker, FT Korkmaz, A Ramanujan
Nature Communications, 2021nature.com
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 …
Abstract
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.
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