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A distal Foxp3 enhancer enables interleukin-2 dependent thymic Treg cell lineage commitment for robust immune tolerance[ChIP-seq][Stat5]

ABSTRACT: A distal Foxp3 enhancer enables interleukin-2 dependent thymic Treg cell lineage commitment for robust immune tolerance[ChIP-seq][Stat5]

PROVIDER: PRJNA687483 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13362486.fastq.gz	Fastqsanger.gz
	SRR13362487.fastq.gz	Fastqsanger.gz
	SRR13362488.fastq.gz	Fastqsanger.gz
	SRR13362489.fastq.gz	Fastqsanger.gz

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Similar Datasets

A distal Foxp3 enhancer enables interleukin-2 dependent thymic Treg cell lineage commitment for robust immune tolerance[ChIP-seq][Stat5]

Project description:STAT5 activation downstream of the Interleukin-2 receptor (IL-2R) facilitates Foxp3 expression, which is required for the differentiation and function of regulatory T (Treg) cells. However, due to the pleiotropic roles of IL-2R signaling, it is unclear how STAT5 acts on the Foxp3 locus to promote Treg cell lineage commitment. Here, we report that IL-2–STAT5 signaling converges on an enhancer (CNS4) during early Foxp3 induction. CNS4 facilitates and sustains the IL-2–dependent CD25+Foxp3– precursor to Treg cell transition in the thymus. Its deficiency results in markedly impaired Treg cell generation in neonates, which is partially mitigated with age. While the thymic Treg cell paucity caused by CNS4 deficiency did not result in autoimmunity on its own, it exacerbated autoimmune manifestations caused by disruption of the Aire gene. Thus, CNS4 enhancer activity ensures robust Treg cell differentiation early in postnatal life and, cooperatively with other tolerance mechanisms, minimizes autoimmunity.

2021-03-16 | GSE163760 | GEO

A distal Foxp3 enhancer enables interleukin-2 dependent thymic Treg cell lineage commitment for robust immune tolerance[TCR-seq]

2021-03-16 | GSE164117 | GEO

A distal Foxp3 enhancer enables interleukin-2 dependent thymic Treg cell lineage commitment for robust immune tolerance

Project description:STAT5 transcription factor activation downstream of the Interleukin-2 receptor (IL-2R) induces expression of Foxp3, a critical step in the differentiation of regulatory T (Treg) cells. Due to the pleiotropic outputs of IL-2R signaling, it is unclear whether STAT5 acts directly on the Foxp3 locus to promote its expression . Here, we report that IL-2 – STAT5 signaling converged on an enhancer (CNS4) during Foxp3 induction. CNS4 facilitated and sustained the IL-2 dependent CD25+Foxp3– precursor to Treg cell transition in the thymus. Its deficiency resulted in markedly impaired Treg cell generation in neonates, which was partially mitigated with age. While the thymic Treg cell paucity caused by CNS4 deficiency did not result in autoimmunity on its own, it exacerbated autoimmune manifestations caused by disruption of the Aire gene. Thus, CNS4 enhancer activity ensures robust Treg cell differentiation early in postnatal life and cooperatively with other tolerance mechanisms, minimizes autoimmunity.

2021-03-16 | GSE168942 | GEO

A distal Foxp3 enhancer enables interleukin-2 dependent thymic Treg cell lineage commitment for robust immune tolerance [ATAC-Seq]

2021-03-17 | GSE169043 | GEO

A distal Foxp3 enhancer enables interleukin-2 dependent thymic Treg cell lineage commitment for robust immune tolerance [RNA-seq]

2021-03-16 | GSE168829 | GEO

A distal Foxp3 enhancer enables interleukin-2 dependent thymic Treg cell lineage commitment for robust immune tolerance.

Project description:Activation of the STAT5 transcription factor downstream of the Interleukin-2 receptor (IL-2R) induces expression of Foxp3, a critical step in the differentiation of regulatory T (Treg) cells. Due to the pleiotropic effects of IL-2R signaling, it is unclear how STAT5 acts directly on the Foxp3 locus to promote its expression. Here, we report that IL-2 - STAT5 signaling converged on an enhancer (CNS0) during Foxp3 induction. CNS0 facilitated the IL-2 dependent CD25+Foxp3- precursor to Treg cell transition in the thymus. Its deficiency resulted in impaired Treg cell generation in neonates, which was partially mitigated with age. While the thymic Treg cell paucity caused by CNS0 deficiency did not result in autoimmunity on its own, it exacerbated autoimmune manifestations caused by disruption of the Aire gene. Thus, CNS0 enhancer activity ensures robust Treg cell differentiation early in postnatal life and cooperatively with other tolerance mechanisms minimizes autoimmunity.

| S-EPMC8317508 | biostudies-literature

A distal Foxp3 enhancer enables interleukin-2 dependent thymic Treg cell lineage commitment for robust immune tolerance

Project description:A distal Foxp3 enhancer enables interleukin-2 dependent thymic Treg cell lineage commitment for robust immune tolerance

| PRJNA714640 | ENA

A distal Foxp3 enhancer enables interleukin-2 dependent thymic Treg cell lineage commitment for robust immune tolerance

Project description:A distal Foxp3 enhancer enables interleukin-2 dependent thymic Treg cell lineage commitment for robust immune tolerance

| PRJNA688916 | ENA

Defining STAT5 target genes in thymic precursor cells at pre- and post-commitment stages

Project description:STAT5 is critical for inducing lineage specifying transcription factors, establishing effector gene programs, upregulating IL-2Rα (also known as CD25), and supporting cell survival in response to environmental cues in mature T cells. Although it has been shown that IL-7-induced STAT5 signaling is also essential for survival of thymic precursor cells, the exact roles of STAT5A and STAT5B and their target genes that contribute to the developmental program in early thymic development have been unknown. To define STAT5 target genes in these early T-cell progenitors, we have performed CRISPR-Cas9 mediated acute deletion of Stat5a and Stat5b in combination. We first carried out preliminary experiments to determine the stages in which IL-7 could induce maximal STAT5 phosphorylation in thymic double negative (DN) cells (B. Shin, unpublished data). We then focused on genes responding to loss of STAT5 in two different stages: CD25+ Bcl11b- pre-commitment stage, and CD25+ Bcl11b+ post-commitment stage. Of note, to generate these early pro-T cells in OP9-DLL1 coculture, we exploited bone-marrow precursor cells expressing a Bcl2 transgene to minimize survival defects due to loss of STAT5A and STAT5B. Our data show that STAT5 is necessary, in both pre- and post-commitment stages, for optimal expression of the IL-2Rα gene (Il2ra), which is constitutively expressed in normal DN2 and DN3 pro-T cells. This dataset further defines a distinct set of additional genes responding more strongly to loss of STAT5 in pro-T cells. The linked manuscript by R. Spolski et al. and other datasets referenced therein include data documenting the genomic occupancy of STAT5B in corresponding stages. In summary, our data define STAT5-responsive target genes during early T development.

2023-10-16 | GSE184845 | GEO

A distal Foxp3 enhancer enables interleukin-2 dependent thymic Treg cell lineage commitment for robust immune tolerance[TCR-seq]

Project description:A distal Foxp3 enhancer enables interleukin-2 dependent thymic Treg cell lineage commitment for robust immune tolerance[TCR-seq]

| PRJNA688919 | ENA

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