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Antigen presentation by lung epithelial cells directs CD4+ TRM cell function and regulates barrier immunity
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Antigen presentation by lung epithelial cells directs CD4+ TRM cell function and regulates barrier immunity
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Journal Article
Antigen presentation by lung epithelial cells directs CD4+ TRM cell function and regulates barrier immunity
2021
Overview
Barrier tissues are populated by functionally plastic CD4
+
resident memory T (T
RM
) cells. Whether the barrier epithelium regulates CD4
+
T
RM
cell locations, plasticity and activities remains unclear. Here we report that lung epithelial cells, including distinct surfactant protein C (SPC)
low
MHC
high
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
+
T
RM
cells. Recurrent encounters with cognate antigen in the absence of epithelial MHC-II leads CD4
+
T
RM
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
+
T
RM
cell phenotypes. Thus, we establish epithelial antigen presentation as a critical regulator of CD4
+
T
RM
cell function and identify epithelial-CD4
+
T
RM
cell immune interactions as core elements of barrier immunity.
The maintenance of T resident memory (T
RM
) cells within pulmonary tissues is incompletely understood. Here the authors show that antigen presentation by lung epithelial cells maintains function and phenotype of pulmonary T
RM
cells within specific locational niches.
