Journal article
Antigen presentation by lung epithelial cells directs CD4 + T RM cell function and regulates barrier immunity
Nature communications, Vol.12(1), p.5834
10/05/2021
DOI: 10.1038/s41467-021-26045-w
PMCID: PMC8492657
PMID: 34611166
Abstract
Barrier tissues are populated by functionally plastic CD4
resident memory T (T
) cells. Whether the barrier epithelium regulates CD4
T
cell locations, plasticity and activities remains unclear. Here we report that lung epithelial cells, including distinct surfactant protein C (SPC)
MHC
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
cells. Recurrent encounters with cognate antigen in the absence of epithelial MHC-II leads CD4
T
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
cell phenotypes. Thus, we establish epithelial antigen presentation as a critical regulator of CD4
T
cell function and identify epithelial-CD4
T
cell immune interactions as core elements of barrier immunity.
Details
- Title: Subtitle
- Antigen presentation by lung epithelial cells directs CD4 + T RM cell function and regulates barrier immunity
- Creators
- Anukul T Shenoy - Boston UniversityCarolina Lyon De Ana - Boston University School of MedicineEmad I Arafa - Boston UniversityIsabelle Salwig - Max Planck Institute for Heart and Lung ResearchKimberly A Barker - Boston UniversityFiliz T Korkmaz - Boston UniversityAditya Ramanujan - Boston UniversityNeelou S Etesami - Boston UniversityAlicia M Soucy - Boston UniversityIan M C Martin - Boston University School of MedicineBrian R Tilton - Boston UniversityAnne Hinds - Boston UniversityWesley N Goltry - Boston UniversityHasmeena Kathuria - Boston UniversityThomas Braun - Max Planck Institute for Heart and Lung ResearchMatthew R Jones - Boston UniversityLee J Quinton - Boston UniversityAnna C Belkina - Boston UniversityJoseph P Mizgerd - Boston University
- Resource Type
- Journal article
- Publication Details
- Nature communications, Vol.12(1), p.5834
- DOI
- 10.1038/s41467-021-26045-w
- PMID
- 34611166
- PMCID
- PMC8492657
- eISSN
- 2041-1723
- Grant note
- R01 AI115053 / NIAID NIH HHS R01 HL111449 / NHLBI NIH HHS R35 HL135756 / NHLBI NIH HHS F32 HL147461 / NHLBI NIH HHS R01 HL136725 / NHLBI NIH HHS R33 HL137081 / NHLBI NIH HHS R01 GM120060 / NIGMS NIH HHS T32 HL007035 / NHLBI NIH HHS F31 HL142199 / NHLBI NIH HHS R61 HL137081 / NHLBI NIH HHS F31 HL147397 / NHLBI NIH HHS
- Language
- English
- Date published
- 10/05/2021
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984696755302771
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