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Series GSE84820 Query DataSets for GSE84820
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.
Overall design Transcriptional profiling of T cells in mice with chronic and acute infections using RNA sequencing
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
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)
GSM2251838 Irf4Het Acute d30 REP1
GSM2251839 Irf4Het Chronic d30 REP1
GSM2251840 WT Acute d30 REP1
BioProject PRJNA335368
SRA SRP079900

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Supplementary file Size Download File type/resource
GSE84820_RAW.tar 8.9 Mb (http)(custom) TAR (of TXT)
GSE84820_Raw_counts.txt.gz 1.1 Mb (ftp)(http) TXT
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Raw data are available in SRA
Processed data provided as supplementary file

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