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| Status |
Public on Jun 27, 2013 |
| Title |
Bach2 represses effector programmes to stabilize Treg-mediated immune homeostasis |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Through their functional diversification, CD4+ T cells play key roles in both driving and constraining immune-mediated pathology. Transcription factors are critical in the generation and maintenance of cellular diversity and negative regulators antagonistic to alternate fates often act in conjunction with positive regulators to stabilize lineage specification1. Polymorphisms within the locus encoding a transcription factor BACH2 are associated with diverse immune-mediated diseases including asthma2, multiple sclerosis3, Crohn¹s disease4-5, coeliac disease6, vitiligo7 and type 1 diabetes8. A role for Bach2 in maintaining immune homeostasis, however, has not been established. Here, we define Bach2 as a broad regulator of immune activation that stabilizes immunoregulatory capacity while repressing the differentiation programmes of multiple effector lineages in CD4+ T cells. Bach2 was required for efficient formation of regulatory (Treg) cells and consequently for suppression of lethal inflammation in a manner that was Treg cell dependent. Assessment of the genome-wide function of Bach2, however, revealed that it represses genes associated with effector cell differentiation. Consequently, its absence during Treg polarization resulted in inappropriate diversion to effector lineages. In addition, Bach2 constrained full effector differentiation within Th1, Th2 and Th17 cell lineages. These findings identify Bach2 as a key regulator of CD4+ T-cell differentiation that prevents inflammatory disease by controlling the balance between tolerance and immunity.
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| Overall design |
The role of Bach2t to regulate immune homeostasis was investigated by mapping DNA binding profiles of Bach2 in iTreg condition.
The function of Bach2 was also evaluated by comparing transcriptome in WT and Bach2-deficient iTreg cells and further comparison was done with transcriptome in naive, Th1, Th2, and Th17 conditions.
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| Contributor(s) |
Roychoudhuri R, Hirahara K, Mousavi K, Zare H, Vahedi G, Sun H, Takahashi H, Sartorelli V, Kanno Y, O'Shea JJ, Restifo NP |
| Citation(s) |
23728300 |
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| Submission date |
Apr 11, 2013 |
| Last update date |
May 15, 2019 |
| Contact name |
Golnaz Vahedi |
| Organization name |
National Institutes of Health
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| Department |
NIAMS
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| Lab |
Lymphocyte Cell Biology Section
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| Street address |
9000 Rockville Pike Bldg 10 Rm 13C101A
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| City |
Bethesda |
| State/province |
MD |
| ZIP/Postal code |
20892 |
| Country |
USA |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA196832 |
| SRA |
SRP020940 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE45975_RAW.tar |
12.6 Mb |
(http)(custom) |
TAR (of RPKM, TXT, WIG) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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