|
| Status |
Public on Jan 25, 2016 |
| Title |
Autophagy enforces functional integrity of regulatory T cells by coupling environmental cues and metabolic homeostasis |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
Regulatory T (Treg) cells respond to immune and inflammatory signals to mediate immunosuppression, but how the functional integrity of Treg cells is maintained under activating environments is unclear. Here we show that autophagy is active in Treg cells and supports their lineage stability and survival fitness. Treg cell–specific deletion of Atg7 or Atg5, both essential genes in autophagy, leads to loss of Treg cells, greater tumor resistance and development of inflammatory disorders. Atg7-deficient Treg cells show increased apoptosis and readily lose expression of the transcription factor Foxp3, especially after activation. Mechanistically, autophagy deficiency upregulates mTORC1 and c-Myc and glycolytic metabolism, which contributes to defective Treg function. Therefore, autophagy couples environmental signals and metabolic homeostasis to protect lineage and survival integrity of Treg cells in activating contexts.
|
| |
|
| Overall design |
We used microarrays to explore the gene expression profiles differentially expressed in CD4+Foxp3-YFP+ Treg cells from untreated and rapamycin-treated Atg7+/- (Atg7-het; Atg7 +/fl crossed with Foxp3-Cre) and Atg7-/- (Atg7-KO; Atg7 fl/fl mice crossed with Foxp3-Cre) mice
|
| |
|
| Contributor(s) |
Wei J, Neale G, Chi H |
| Citation(s) |
26808230 |
| Submission date |
Nov 19, 2015 |
| Last update date |
Feb 21, 2018 |
| Contact name |
Geoffrey Neale |
| E-mail(s) |
geoffrey.neale@stjude.org
|
| Organization name |
St Jude Childrens Research Hospital
|
| Department |
Hartwell Center
|
| Street address |
262 Danny Thomas Place
|
| City |
Memphis |
| State/province |
TN |
| ZIP/Postal code |
38105 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL16570 |
[MoGene-2_0-st] Affymetrix Mouse Gene 2.0 ST Array [transcript (gene) version] |
|
| Samples (16)
|
| GSM1945889 |
Atg7+/- Treg cells untreated replicate 1 |
| GSM1945890 |
Atg7+/- Treg cells untreated replicate 2 |
| GSM1945891 |
Atg7+/- Treg cells untreated replicate 3 |
| GSM1945892 |
Atg7+/- Treg cells untreated replicate 4 |
| GSM1945893 |
Atg7-/- Treg cells untreated replicate 1 |
| GSM1945894 |
Atg7-/- Treg cells untreated replicate 2 |
| GSM1945895 |
Atg7-/- Treg cells untreated replicate 3 |
| GSM1945896 |
Atg7-/- Treg cells untreated replicate 4 |
| GSM1945897 |
Atg7+/- Treg cells rapamycin treated replicate 1 |
| GSM1945898 |
Atg7+/- Treg cells rapamycin treated replicate 2 |
| GSM1945899 |
Atg7+/- Treg cells rapamycin treated replicate 3 |
| GSM1945900 |
Atg7+/- Treg cells rapamycin treated replicate 4 |
| GSM1945901 |
Atg7-/- Treg cells rapamycin treated replicate 1 |
| GSM1945902 |
Atg7-/- Treg cells rapamycin treated replicate 2 |
| GSM1945903 |
Atg7-/- Treg cells rapamycin treated replicate 3 |
| GSM1945904 |
Atg7-/- Treg cells rapamycin treated replicate 4 |
|
| Relations |
| BioProject |
PRJNA302814 |
Less...
More...