Transcriptomics,Genomics,Multiomics

Dataset Information

4

Transcription profiling by high throughput sequencing of induced regulatory T cells from Bach2-deficient mice


ABSTRACT: 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. 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.

OTHER RELATED OMICS DATASETS IN: PRJNA196832PRJNA182359

ORGANISM(S): Mus musculus  

SUBMITTER: Vittorio Sartorelli   Kambiz Mousavi  John J O'Shea  Hossein Zare  Hongwei Sun  Yuka Kanno  Rahul Roychoudhuri  Hayato Takahashi  Kiyoshi Hirahara  Nicholas P Restifo  Golnaz Vahedi 

PROVIDER: E-GEOD-45975 | ArrayExpress | 2013-06-27

SECONDARY ACCESSION(S): GSE45975SRP020940PRJNA196832

REPOSITORIES: GEO, ArrayExpress, ENA

Dataset's files

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E-GEOD-45975.idf.txt Idf
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Publications


Through their functional diversification, distinct lineages of CD4(+) T cells can act to either drive or constrain immune-mediated pathology. Transcription factors are critical in the generation of cellular diversity, and negative regulators antagonistic to alternate fates often act in conjunction with positive regulators to stabilize lineage commitment. Genetic polymorphisms within a single locus encoding the transcription factor BACH2 are associated with numerous autoimmune and allergic diseas  ...[more]

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