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| Status |
Public on May 16, 2018 |
| Title |
Transcriptional profiles of miR-155 overexpressing CD8T cells during chronic infection |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Persistent viral infections and tumors drive development of exhausted T (TEX) cells. In these settings, TEX cells establish an important host-pathogen or host-tumor stalemate. However, TEX cells erode over time, leading to loss of pathogen or cancer containment. We identified microRNA (miR)-155 as a key regulator of sustained TEX cell responses during chronic lymphocytic choriomeningitis virus (LCMV) infection. Genetic deficiency of miR-155 ablated CD8 T cell responses during chronic infection. Conversely, enhanced miR-155 expression promoted expansion and long-term persistence of TEX cells. However, rather than strictly antagonizing exhaustion, miR-155 promoted a terminal TEX cell subset. Transcriptional profiling identified coordinated control of cell signaling and transcription factor pathways, including the key AP-1 family member Fosl2. Overexpression of Fosl2 reversed the miR-155 effects, identifying a link between miR-155 and the AP-1 transcriptional program in regulating TEX cells. Thus, we identify a mechanism of miR-155 regulation of TEX cells and a key role for Fosl2 in T cell exhaustion.
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| Overall design |
RNA-Seq analysis was used to investigate how miR-155 affects the expansion and differentiation of CD8 Tcells during chronic infection
12 samples from 4 groups, 3 replicates each
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| Contributor(s) |
STELEKATI E, Wherry EJ |
| Citation(s) |
29768211 |
| Submission date |
May 15, 2018 |
| Last update date |
Feb 25, 2019 |
| Contact name |
E JOHN WHERRY |
| Organization name |
University of Pennsylvania
|
| Department |
Systems Pharmacology and Translational Therapeutics,Institute for Immunology
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| Street address |
421 Curie Blvd,354 BRB II/III
|
| City |
Philadelphia |
| State/province |
PA |
| ZIP/Postal code |
19104 |
| Country |
USA |
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| Platforms (1) |
| GPL15103 |
Illumina HiSeq 1000 (Mus musculus) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA471517 |
| SRA |
SRP146079 |
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