|
| Status |
Public on Dec 27, 2012 |
| Title |
Comparison of RelB-/- and RelB+/- thymi |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
Thymic medullary epithelial cell (mTEC) expression of the autoimmune regulator AIRE, and of tissue-specific antigens, is controlled by members of the non-canonical NF-kB signalling pathway, including RelB and NF-kB2. Of the genes in this pathway, RelB-/- mice develop a particularly severe multi-organ autoimmune syndrome, resembling Foxp3-deficiency. RelB-/- mice have medullary atrophy and few mTECs but the mechanism is unknown. We show that RelB is required for expression of medullary chemokines and mTEC AIRE, selection of a diverse peripheral T cell repertoire, and for peripheral Foxp3+ Treg function. Vβ families of T cells infiltrating diseased peripheral organs and thymic Treg were similarly skewed. Surprisingly, medullary atrophy results from intra-thymic granulocyte infiltration, consequent upon the Th2-mediated autoimmune disease. Dominant tolerance corrects thymic inflammatory disease and loss of thymic function. We demonstrate a reversible RelB-dependent inflammatory mechanism for loss of central tolerance associated with medullary atrophy.
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| Overall design |
Thymi from 4 RelB+/- mice and 3 RelB-/- mice were profiled by microarays
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| Contributor(s) |
O'Sullivan BJ |
| Citation missing |
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| |
| Submission date |
Dec 26, 2012 |
| Last update date |
Jun 14, 2018 |
| Contact name |
Brendan John O'Sullivan |
| Organization name |
The University of Queensland Diamantina Institute Translational Research Institute
|
| Street address |
Level 6, 37 Kent Street Woolloongabba
|
| City |
Brisbane |
| State/province |
Queensland |
| ZIP/Postal code |
4102 |
| Country |
Australia |
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| Platforms (1) |
| GPL6885 |
Illumina MouseRef-8 v2.0 expression beadchip |
|
| Samples (7)
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| Relations |
| BioProject |
PRJNA184731 |
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