|
| Status |
Public on Jan 01, 2018 |
| Title |
Metabolic exhaustion of T cells in chronic infection is mediated by inhibitory receptor PD-1 and T cell receptor dependent transcription factor IRF4 |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
During chronic stimulation T cells acquire an exhausted phenotype characterized by expression of multiple inhibitory receptors and down-modulation of effector function. While this is required for the protection of the organism from excessive immunopathology, it also prevents successful immunity against persistent viruses or tumor cells. Here we demonstrate that CD8+ T cell exhaustion is characterized by a progressive decline in cellular metabolism. Exhausted T cells exhibit reduced metabolic reserve, impaired fatty acid oxidation and production of mitochondrial reactive oxygen species (ROS). Blockade of inhibitory PD-1/PD-L1 signaling rescued mitochondrial biogenesis, oxidative phosphorylation and ROS production, which was required for efficient restoration of cellular expansion and effector function. Expression of inhibitory receptors and impaired metabolic function was fuled by high amounts of IRF4, BATF and NFAT, which formed a TCR-responsive transcriptional circuit that sustained the transcriptional network responsible for T cell exhaustion.
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| |
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| Overall design |
Transcriptional profiling of T cells in mice with chronic and acute infections using RNA sequencing
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| |
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| Contributor(s) |
Man K, liao Y, Shi W, Kallies A |
| Citation(s) |
29246443 |
| Submission date |
Jul 25, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Wei Shi |
| E-mail(s) |
Wei.Shi@onjcri.org.au
|
| Organization name |
Olivia Newton John Cancer Research Institute
|
| Department |
Bioinformatics and Cancer Genomics
|
| Street address |
Level 5, ONJ Cancer Centre, 145 Studley Rd
|
| City |
Heidelberg |
| State/province |
VIC |
| ZIP/Postal code |
3084 |
| Country |
Australia |
| |
|
| Platforms (2) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
|
| Samples (37)
|
|
| Relations |
| BioProject |
PRJNA335368 |
| SRA |
SRP079900 |
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