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

Anukul T. Shenoy, Carolina Lyon De Ana, Emad I. Arafa, Isabelle Salwig, Kimberly A. Barker, Filiz T. Korkmaz, Aditya Ramanujan, Neelou S. Etesami, Alicia M. Soucy, Ian M. C. Martin, Brian R. Tilton, Anne Hinds, Wesley N. Goltry, Hasmeena Kathuria, Thomas Braun, Matthew R. Jones, Lee J. Quinton, Anna C. Belkina and Joseph P. Mizgerd ()
Additional contact information
Anukul T. Shenoy: Pulmonary Center, Boston University School of Medicine
Carolina Lyon De Ana: Pulmonary Center, Boston University School of Medicine
Emad I. Arafa: Pulmonary Center, Boston University School of Medicine
Isabelle Salwig: Max-Planck-Institute for Heart and Lung Research, Member of the German Center for Lung Research (DZL)
Kimberly A. Barker: Pulmonary Center, Boston University School of Medicine
Filiz T. Korkmaz: Pulmonary Center, Boston University School of Medicine
Aditya Ramanujan: Pulmonary Center, Boston University School of Medicine
Neelou S. Etesami: Pulmonary Center, Boston University School of Medicine
Alicia M. Soucy: Pulmonary Center, Boston University School of Medicine
Ian M. C. Martin: Pulmonary Center, Boston University School of Medicine
Brian R. Tilton: Flow Cytometry Core Facility, Boston University School of Medicine
Anne Hinds: Pulmonary Center, Boston University School of Medicine
Wesley N. Goltry: Pulmonary Center, Boston University School of Medicine
Hasmeena Kathuria: Pulmonary Center, Boston University School of Medicine
Thomas Braun: Max-Planck-Institute for Heart and Lung Research, Member of the German Center for Lung Research (DZL)
Matthew R. Jones: Pulmonary Center, Boston University School of Medicine
Lee J. Quinton: Pulmonary Center, Boston University School of Medicine
Anna C. Belkina: Pulmonary Center, Boston University School of Medicine
Joseph P. Mizgerd: Pulmonary Center, Boston University School of Medicine

Nature Communications, 2021, vol. 12, issue 1, 1-16

Abstract: 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)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.

Date: 2021
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DOI: 10.1038/s41467-021-26045-w

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