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| Status |
Public on Aug 28, 2017 |
| Title |
The TNF receptor super family - NF-κB axis is critical to maintain effector regulatory T cells in lymphoid and non-lymphoid tissues [ChIP-seq] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
After exiting the thymus, Foxp3+ regulatory T (Treg) cells undergo further differentiation in the periphery resulting in the generation of effector (e)Treg cells, a process dependent on TCR signaling and the transcription factor IRF4. Here we show tumor necrosis factor receptor super family (TNFRSF) signaling plays a crucial role in the development and maintenance of eTreg cells. TNFRSF signaling activated the NF-κB transcription factor RelA and induced expansion and survival of eTreg cells in lymphoid and non-lymphoid tissues, including RORγt+ resident Treg cells in the small intestine. RelA regulated basic cellular processes in Treg cells, including cell survival and proliferation in response to TNFRSF signaling, but was not required for IRF4 expression or DNA binding, indicating that both pathways operate independently. Importantly, a similar pathway appeared to be active in humans, as patients with a point mutation in NF-κB1, a binding partner of RelA, had severely compromised Treg cells. Therefore, although TCR signaling is essential for eTreg cell differentiation, the TNFRSF-NF-κB axis was additionally required in a non-redundant manner to maintain the pool of eTreg cells.
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| |
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| Overall design |
Identification of IRF4 and RelA/p65 target genes in murine regulatory T cells.
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| |
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| Contributor(s) |
Vasanthakumar A, Liao Y, Shi W, Kallies A |
| Citation(s) |
28889989 |
| |
| Submission date |
Apr 26, 2017 |
| Last update date |
May 15, 2019 |
| Contact name |
Wei Shi |
| E-mail(s) |
Wei.Shi@onjcri.org.au
|
| Organization name |
Olivia Newton John Cancer Research Institute
|
| Department |
Bioinformatics and Cancer Genomics
|
| Street address |
Level 5, ONJ Cancer Centre, 145 Studley Rd
|
| City |
Heidelberg |
| State/province |
VIC |
| ZIP/Postal code |
3084 |
| Country |
Australia |
| |
|
| Platforms (2) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
|
| Samples (7)
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| This SubSeries is part of SuperSeries: |
| GSE98264 |
The TNF receptor super family - NF-κB axis is critical to maintain effector regulatory T cells in lymphoid and non-lymphoid tissues |
|
| Relations |
| BioProject |
PRJNA384489 |
| SRA |
SRP105382 |
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