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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Aug 04, 2017 |
| Title |
Critical roles of mTORC1 and mTORC2 kinase signaling and glucose metabolism in follicular helper T cell differentiation |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
AbstractFollicular helper T (Tfh) cells are crucial for germinal center (GC) formation and humoral adaptive immunity. Mechanisms underlying Tfh cell differentiation in peripheral and mucosal lymphoid organs are incompletely understood. We report here that mTOR kinase complexes 1 and 2 (mTORC1 and mTORC2) are essential for Tfh cell differentiation and GC reaction under steady state and after antigen immunization and viral infection. Loss of mTORC1 and mTORC2 in T cells exerted distinct effects on Tfh cell signature gene expression, whereas increased mTOR activity promoted Tfh responses. Deficiency of mTORC2 impaired CD4+ T cell accumulation and IgA production, and aberrantly induced Foxo1 transcription factor. Mechanistically, the costimulatory molecule ICOS activated mTORC1 and mTORC2 to drive glycolysis and lipogenesis, and Glut1-mediated glucose metabolism promoted Tfh cell responses. Altogether, mTOR acts as a central node in Tfh cells to link immune signals to glucose metabolism and transcriptional activity.
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| Overall design |
We used micorarrays to compare the global transcription profile in CD4+CD25-CD44+CD62L- T cells from Peyer's patch of WT, Raptor-/- (Cd4cre x Raptorfl/fl mice), or Rictor-/- (Cd4cre x Rictorfl/fl mice) mice.
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| Contributor(s) |
Zeng H, Neale G, Chi H |
| Citation(s) |
27637146 |
| Submission date |
Aug 12, 2016 |
| Last update date |
Feb 21, 2018 |
| Contact name |
Geoffrey Neale |
| E-mail(s) |
geoffrey.neale@stjude.org
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| Organization name |
St Jude Childrens Research Hospital
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| Department |
Hartwell Center
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| Street address |
262 Danny Thomas Place
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| City |
Memphis |
| State/province |
TN |
| ZIP/Postal code |
38105 |
| Country |
USA |
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| Platforms (1) |
| GPL16570 |
[MoGene-2_0-st] Affymetrix Mouse Gene 2.0 ST Array [transcript (gene) version] |
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| Samples (12)
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| GSM2277124 |
WT T cells (Cd4cre- / Raptor fl/fl), replicate 1 |
| GSM2277125 |
WT T cells (Cd4cre- / Raptor fl/fl), replicate 2 |
| GSM2277126 |
WT T cells (Cd4cre- / Rictor fl/fl), replicate 3 |
| GSM2277127 |
WT T cells (Cd4cre- / Rictor fl/fl), replicate 4 |
| GSM2277128 |
WT T cells (Cd4cre- / Rictor fl/fl), replicate 5 |
| GSM2277129 |
Rictor -/- T cells (Cd4cre+ / Rictor fl/fl), replicate 1 |
| GSM2277131 |
Rictor -/- T cells (Cd4cre+ / Rictor fl/fl), replicate 2 |
| GSM2277132 |
Rictor -/- T cells (Cd4cre+ / Rictor fl/fl), replicate 3 |
| GSM2277133 |
Rictor -/- T cells (Cd4cre+ / Rictor fl/fl), replicate 4 |
| GSM2277134 |
Raptor -/- T cells (Cd4cre+ / Raptor fl/fl), replicate 1 |
| GSM2277136 |
Raptor -/- T cells (Cd4cre+ / Raptor fl/fl), replicate 2 |
| GSM2277138 |
Raptor -/- T cells (Cd4cre+ / Raptor fl/fl), replicate 3 |
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| Relations |
| BioProject |
PRJNA338784 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE85555_RAW.tar |
102.8 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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