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

Autor: Shenoy, Anukul T., Lyon De Ana, Carolina, Arafa, Emad I., Salwig, Isabelle, Barker, Kimberly A., Korkmaz, Filiz T., Ramanujan, Aditya, Etesami, Neelou S., Soucy, Alicia M., Martin, Ian M. C., Tilton, Brian R., Hinds, Anne, Goltry, Wesley N., Kathuria, Hasmeena, Braun, Thomas, Jones, Matthew R., Quinton, Lee J., Belkina, Anna C., Mizgerd, Joseph P.
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Zdroj: Nature Communications; 10/5/2021, Vol. 12 Issue 1, p1-16, 16p
Abstrakt: 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. The maintenance of T resident memory (TRM) cells within pulmonary tissues is incompletely understood. Here the authors show that antigen presentation by lung epithelial cells maintains function and phenotype of pulmonary TRM cells within specific locational niches. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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