1. Antigen presentation by lung epithelial cells directs CD4 + T RM cell function and regulates barrier immunity.
- Author
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Shenoy AT, Lyon De Ana C, Arafa EI, Salwig I, Barker KA, Korkmaz FT, Ramanujan A, Etesami NS, Soucy AM, Martin IMC, Tilton BR, Hinds A, Goltry WN, Kathuria H, Braun T, Jones MR, Quinton LJ, Belkina AC, and Mizgerd JP
- Subjects
- Animals, CD4-Positive T-Lymphocytes metabolism, Flow Cytometry, Fluorescent Antibody Technique, Leukocytes cytology, Leukocytes metabolism, Lung metabolism, Mice, Mice, Inbred C57BL, Microscopy, Electron, Transmission, Real-Time Polymerase Chain Reaction, Antigen Presentation physiology, Epithelial Cells metabolism, Lung cytology
- 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)low MHChigh 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., (© 2021. The Author(s).)- Published
- 2021
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