|
| Status |
Public on Jun 14, 2018 |
| Title |
RNAseq of Wild Type and IL27ra KO CD8+ Tumor infiltrating lymphocytes isolated from B16F10 melanoma. |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Expression of co-inhibitory receptors, such as CTLA-4 and PD-1, on effector T cells is a key mechanism for ensuring immune homeostasis. Dysregulated co-inhibitory receptor expression on CD4+ T cells promotes autoimmunity while sustained overexpression on CD8+ T cells promotes T cell dysfunction or exhaustion, leading to impaired ability to clear chronic viral infections and cancer. Here, we used RNA and protein expression profiling at single-cell resolution to identify a module of co-inhibitory receptors that includes not only several known co-inhibitory receptors (PD-1, Tim-3, Lag-3, and TIGIT), but also a number of novel surface receptors. We functionally validated two novel co-inhibitory receptors, Activated protein C receptor (Procr) and Podoplanin (Pdpn). The module of co-inhibitory receptors is co-expressed in both CD4+ and CD8+ T cells and is part of a larger co-inhibitory gene program that is shared by non-responsive T cells in multiple physiological contexts and is driven by the immunoregulatory cytokine IL-27. Computational analysis identified the transcription factors Prdm1 and c-Maf as cooperative regulators of the co-inhibitory module, which we validated experimentally. This molecular circuit underlies the co-expression of co-inhibitory receptors in T cells and identifies novel regulators of T cell function with the potential to regulate autoimmunity and tumor immunity.
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| |
|
| Overall design |
RNAseq analysis of IL-27 dependent CD8 T cell gene signature in the tumor.
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| |
|
| Contributor(s) |
Madi A |
| Citation(s) |
29899446 |
| |
| Submission date |
Apr 16, 2018 |
| Last update date |
Mar 21, 2019 |
| Contact name |
Asaf Madi |
| E-mail(s) |
[email protected]
|
| Organization name |
BWH
|
| Department |
Neurology
|
| Lab |
Ana Carrizosa Anderson
|
| Street address |
60 Fenwood Road, BTM 10016F
|
| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02115 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
|
| Samples (9)
|
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| This SubSeries is part of SuperSeries: |
| GSE113968 |
The induction and transcriptional regulation of the co-inhibitory gene module in T cells by IL-27 |
|
| Relations |
| BioProject |
PRJNA450427 |
| SRA |
SRP140543 |
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