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

71Citations
Citations of this article
110Readers
Mendeley users who have this article in their library.

This article is free to access.

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.

References Powered by Scopus

Immune-related adverse events associated with immune checkpoint blockade

3285Citations
N/AReaders
Get full text

Identification of bronchioalveolar stem cells in normal lung and lung cancer

1952Citations
N/AReaders
Get full text

Fatal Toxic Effects Associated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-analysis

1920Citations
N/AReaders
Get full text

Cited by Powered by Scopus

The role of PD-1/PD-L1 and application of immune-checkpoint inhibitors in human cancers

241Citations
N/AReaders
Get full text

CD4<sup>+</sup> T cell memory

121Citations
N/AReaders
Get full text

Mucosal immune responses to infection and vaccination in the respiratory tract

121Citations
N/AReaders
Get full text

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Cite

CITATION STYLE

APA

Shenoy, A. T., Lyon De Ana, C., Arafa, E. I., Salwig, I., Barker, K. A., Korkmaz, F. T., … Mizgerd, J. P. (2021). Antigen presentation by lung epithelial cells directs CD4+ TRM cell function and regulates barrier immunity. Nature Communications, 12(1). https://doi.org/10.1038/s41467-021-26045-w

Readers over time

‘21‘22‘23‘24‘25010203040

Readers' Seniority

Tooltip

PhD / Post grad / Masters / Doc 22

50%

Researcher 16

36%

Professor / Associate Prof. 5

11%

Lecturer / Post doc 1

2%

Readers' Discipline

Tooltip

Immunology and Microbiology 22

47%

Biochemistry, Genetics and Molecular Bi... 15

32%

Medicine and Dentistry 6

13%

Agricultural and Biological Sciences 4

9%

Article Metrics

Tooltip
Mentions
News Mentions: 3
Social Media
Shares, Likes & Comments: 290

Save time finding and organizing research with Mendeley

Sign up for free
0