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.
- Shenoy, A. T.
- Lyon De Ana, C.
- Arafa, E. I.
- Salwig, I.
- Barker, K. A.
- Korkmaz, F. T.
- Ramanujan, A.
- Etesami, N. S.
- Soucy, A. M.
- Martin, I. M. C.
- Tilton, B. R.
- Hinds, A.
- Goltry, W. N.
- Kathuria, H.
- Braun, T.
- Jones, M. R.
- Quinton, L. J.
- Belkina, A. C.
- Mizgerd, J. P.
