| First Author | Shenoy AT | Year | 2021 |
| Journal | Nat Commun | Volume | 12 |
| Issue | 1 | Pages | 5834 |
| PubMed ID | 34611166 | Mgi Jnum | J:313660 |
| Mgi Id | MGI:6787656 | Doi | 10.1038/s41467-021-26045-w |
| Citation | Shenoy AT, et al. (2021) Antigen presentation by lung epithelial cells directs CD4(+) TRM cell function and regulates barrier immunity. Nat Commun 12(1):5834 |
| abstractText | 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)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(+) 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. |
