Abstract
Epithelial antigen presentation regulates CD4+ TRM cell locations, functions and activities
The Journal of immunology (1950), Vol.206(1_Supplement), pp.93-93.07
05/01/2021
DOI: 10.4049/jimmunol.206.Supp.93.07
Abstract
Abstract
Barrier tissues are sentinelled by CD4+ TRM cells with potent anti-microbial activities and considerable lineage plasticity. We hypothesized that local antigen presentation by lung epithelial cells (LECs) instruct CD4+ TRM cell activities. Pneumococcal infections in transgenic mice, flow- and spectral-cytometry, computational biology, and immunofluorescence were used to study this biology. All LECs including a novel alveolar surfactant protein C (SPC)low LEC were adept at antigen presentation. Temporal analysis of LECs for MHC-II and costimulatory/coinhibitory molecules revealed that airway club cells were T-cell stimulatory via CD40 while alveolar LECs expressed T-cell inhibitory PD-L1. This anatomical segregation of LEC antigen presentation correlated with deposition of CD4+ TRM cells around airways such that ablation of LEC MHC-II disrupted CD4+ TRM niches and blockade of CD40 signals prevented accumulation of CD4+ TRM cells. Recurrent memory recalls in absence of LEC MHC-II led to expansion of unconventional CD4+ TRM cells co-expressing classically incompatible lineage-defining transcription factors, changing their cytokine repertoire and leading to dysregulated immunity that phenocopied clinical features of checkpoint blockade therapy. Consequently, a tight correlation between MHC-II and PD-L1 was confirmed in mouse and human LECs. We discovered that LEC MHC-II functions in post-translational trafficking lockstep with PD-L1 to exert its restraints on TRM cell activities. Our results identify epithelial antigen presentation as critical instructors of CD4+ TRM cell locations, phenotypes and activities and establish epithelial-CD4+ TRM cell immunological synapses as key components of barrier immunity.
Details
- Title: Subtitle
- Epithelial antigen presentation regulates CD4+ TRM cell locations, functions and activities
- Creators
- Anukul T. ShenoyEmad I ArafaCarolina Lyon De AnaKimberly A BarkerFiliz T KorkmazAditya RamanujanNeelou S EtesamiIan MC MartinBrian R TiltonAnne HindsWesley N GoltryHasmeena KathuriaMatthew R JonesLee J QuintonAnna C BelkinaJoseph P Mizgerd
- Resource Type
- Abstract
- Publication Details
- The Journal of immunology (1950), Vol.206(1_Supplement), pp.93-93.07
- DOI
- 10.4049/jimmunol.206.Supp.93.07
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Language
- English
- Date published
- 05/01/2021
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984696682802771
Metrics
1 Record Views