BACH2 is repurposed following Treg lineage commitment to drive the functional quiescence and maintenance of resting Treg cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA527220 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:In various tissues, cellular homeostasis is achieved by functionally quiescent stem cells which self renew while giving rise to differentiated progeny. Regulatory T (Treg) cells are composed of functionally quiescent resting Treg (rTreg) cells which differentiate into activated Treg (aTreg) cells upon antigen stimulation. How rTreg cells remain quiescent despite chronic exposure to cognate self- and foreign antigens is unclear. The transcription factor BACH2 is critical for early Treg lineage specification but its function following lineage commitment is unresolved. Here, we show Bach2 is highly expressed in lineage-committed rTreg cells but is downregulated in aTreg cells, and upon inflammation. BACH2 binds to AP-1 sites within Treg genomes and its high expression within rTreg cells functions to restrain their TCR-driven activation and differentiation into aTreg cells. As a consequence, cell-autonomous BACH2 expression is required following Treg lineage commitment for the functional quiescence and long-term maintenance of Treg cell populations and for immune homeostasis. This SuperSeries is composed of the SubSeries listed below.
2020-05-12 | GSE128176 | GEO
Project description:In various tissues, cellular homeostasis is achieved by functionally quiescent stem cells which selfrenew while giving rise to differentiated progeny. Regulatory T (Treg) cells are composed of functionally quiescent resting Treg (rTreg) cells which differentiate into activated Treg (aTreg) cells upon antigen stimulation. How rTreg cells remain quiescent despite chronic exposure to cognate self- and foreign antigens is unclear. The transcription factor BACH2 is critical for early Treg lineage specification but its function following lineage commitment is unresolved. Here, we show Bach2 is highly expressed in lineage-committed rTreg cells but is downregulated in aTreg cells, and upon inflammation. BACH2 binds to AP-1 sites within Treg genomes and its high expression within rTreg cells functions to restrain their TCR-driven activation and differentiation into aTreg cells. As a consequence, cell-autonomous BACH2 expression is required following Treg lineagecommitment for the functional quiescence and long-term maintenance of Treg cell populations and for immune homeostasis.
2020-05-12 | GSE127695 | GEO
Project description: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.
2013-06-27 | E-GEOD-45975 | biostudies-arrayexpress
Project description: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.
2013-06-27 | GSE45975 | GEO
Project description:Differentiation and homeostasis of Foxp3 + regulatory T cells (Tregs) are tightly controlled by the interleukin-2 receptor (IL-2R) signaling, yet the mechanisms governing these processes are incompletely understood. Here we report that transcription factor Bach2 attenuates IL-2R signaling to coordinate Treg differentiation and homeostasis by directly repressed CD25 (IL-2Rα). Thus, Bach2 balances IL-2R signaling to orchestrate development and homeostasis of various Treg subsets.
2021-05-11 | GSE164937 | GEO
Project description:These are the FastQ files used for the RNA-seq analysis of WT and Bach2-deficient splenic Foxp3+ Treg cells.
2020-05-12 | GSE127699 | GEO
Project description: Not available
| S-EPMC7478731 | biostudies-literature
Project description:These are the FastQ files used for scRNA-Seq analysis of WT and Bach2-deficient splenic Foxp3+ Treg cells
2020-05-12 | GSE128175 | GEO
Project description:Through a diversity of functional lineages, cells of the innate and adaptive immune system either drive or constrain immune reactions within tumors. Thus, while the immune system has a powerful ability to recognize and kill cancer cells, this function is often suppressed preventing clearance of disease. The transcription factor (TF) BACH2 controls the differentiation and function of multiple innate and adaptive immune lineages, but its role in regulating tumor immunity is not known. Here, we demonstrate that BACH2 is required to establish immunosuppression within tumors. We found that growth of subcutaneously implanted tumors was markedly impaired in Bach2-deficient mice and coincided with intratumoral activation of both innate and adaptive immunity but was dependent upon adaptive immunity. Analysis of tumor-infiltrating lymphocytes in Bach2-deficient mice revealed high frequencies of CD4+ and CD8+ effector cells expressing the inflammatory cytokine IFN-γ. Lymphocyte activation coincided with reduction in the frequency of intratumoral CD4+ Foxp3+ regulatory T (Treg) cells. Mechanistically, Treg-dependent inhibition of CD8+ T cells was required for BACH2-mediated tumor immunosuppression. These findings demonstrate that BACH2 is a key component of the molecular programme of tumor immunosuppression and identify a new target for development of therapies aimed at reversing immunosuppression in cancer. Analysis of tumor-infiltrating lymphocytes in Bach2-deficient mice revealed high frequencies of CD4+ and CD8+ effector cells expressing the inflammatory cytokine IFN-γ. Lymphocyte activation coincided with reduction in the frequency of intratumoral CD4+ Foxp3+ regulatory T (Treg) cells. Mechanistically, Treg-dependent inhibition of CD8+ T cells was required for BACH2-mediated tumor immunosuppression.
2016-06-01 | E-GEOD-74653 | biostudies-arrayexpress
Project description:Bach2 regulates homeostasis of foxp3+ regulatory T cells and protects against fatal lung disease in mice. Cells from WT and Bach2 KO spleen were isolated. CD4+ CD25+ GITR+ (Treg) cells were sorted by FACS sorting. Total RNAs were extracted from sorted Treg cells using by Rneasy Kit (Qiagen).
2013-11-14 | E-GEOD-52337 | biostudies-arrayexpress