|
| Status |
Public on Feb 13, 2019 |
| Title |
Th1 and T17 activation with and without CB839 treatment |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Activated T cells differentiate into functional subsets which require distinct metabolic programs. Glutaminase (GLS) converts glutamine to glutamate to provide substrate for the tricarboxylic acid cycle and epigenetic reactions and here we identify a key role for GLS in T cell activation and specification. Though GLS-deficiency diminished T cell activation, proliferation and impaired differentiation of Th17 cells, loss of GLS also increased Tbet and Interferon-γ expression and CD4 Th1 and CD8 CTL effector cell differentiation. These changes were mediated by differentially altered gene expression and chromatin accessibility, leading to increased sensitivity of Th1 cells to IL-2 mediated mTORC1 signaling. In vivo, GLS-null T cells failed to drive a Th17-mediated Graft-vs-Host Disease model. Transient inhibition of GLS, however, increased Th1 and CTL T cell numbers in viral and chimeric antigen receptor models. Glutamine metabolism thus has distinct roles to promote Th17 but constrain Th1 and CTL effector cell differentiation.
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| |
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| Overall design |
Cells were treated with glutaminase1 inhibitor or vehicle
|
| |
|
| Contributor(s) |
Johnson M, Rathmell J |
| Citation(s) |
30392958 |
| Submission date |
Mar 23, 2018 |
| Last update date |
Feb 13, 2019 |
| Contact name |
Aguirre A de Cubas |
| E-mail(s) |
a.decubas@vumc.org
|
| Organization name |
Vanderbilt University Medical Center
|
| Department |
Hematology and Oncology
|
| Lab |
Rathmell Lab
|
| Street address |
2220 Pierce Ave
|
| City |
NASHVILLE |
| State/province |
TN |
| ZIP/Postal code |
37232 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL21493 |
Illumina HiSeq 3000 (Mus musculus) |
|
| Samples (12)
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|
| Relations |
| BioProject |
PRJNA445376 |
| SRA |
SRP136315 |
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