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Helios enhances the preferential differentiation of human fetal CD4+ naïve T cells into regulatory T cells [RNA-Seq - induced Treg cells].

ABSTRACT: Helios enhances the preferential differentiation of human fetal CD4+ naïve T cells into regulatory T cells [RNA-Seq - induced Treg cells].

PROVIDER: PRJNA544098 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR9104680.fastq.gz	Fastqsanger.gz
	SRR9104690.fastq.gz	Fastqsanger.gz
	SRR9104700.fastq.gz	Fastqsanger.gz
	SRR9104710.fastq.gz	Fastqsanger.gz
	SRR9104681.fastq.gz	Fastqsanger.gz

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Helios enhances the preferential differentiation of human fetal CD4+ naïve T cells into regulatory T cells [RNA-Seq - induced Treg cells].

Project description:RNA sequencing was used to compare the transcriptome of in vitro differentiated adult and fetal induced Treg (iTreg) cells that were culture with IL-2 alone or supplemented with additional TGFb. Additionally, fetal iTreg cells also had Helios knocked out by CRISPR-Cas9 editing, with paired samples treated with the Helios guide RNA1 (HeliosKO) or with the non-targeting control (HeliosWT). Differential gene expression was assessed using generalised linear model designs. This revealed that fetal iTreg cells retain a expression of Treg-specific signature previously identified to be unregulated in primary ex vivo fetal naive T cells, and this signature was not expressed by adult iTreg cells. Helios expression then regulates the Treg-specific transcriptome within fetal iTreg cells by enhancing upregulation of genes associated with Treg differentiation and function, and repressing genes associated with effector specification and pro-inflammatory function.

2019-11-22 | GSE131589 | GEO

Helios expression defines two distinct populations of Foxp3+ Treg cells

Project description:The transcription factor Helios is expressed in a large subset of Foxp3+ Tregs of both mouse and man. We previously demonstrated that Treg induced in peripheral sites (pTreg) from Foxp3- T conventional (Tconv) cells were Helios- and proposed that Helios is a marker of thymic derived Treg (tTreg). To compare the two Treg subpopulations, we generated Helios-GFP reporter mice and crossed them to Foxp3-RFP reporter mice. The Helios+ Treg population expressed a more activated phenotype and had a higher suppressive capacity in vitro. Both populations expressed a highly demethylated TSDR and both subsets were equivalent in their ability to suppress inflammatory bowel disease in vivo. However, Helios+ Treg more effectively inhibited the proliferation of activated, autoreactive splenocytes from scurfy mice. When Helios+ and Helios- Treg were transferred to lymphoreplete mice, both populations maintained comparable Foxp3 expression, but Foxp3 expression was less stable in Helios- Treg when transferred to lymphopenic mice. Gene expression profiling of the two populations demonstrated a large number of differentially expressed genes and that Helios- Treg subpopulation expressed certain genes normally expressed in CD4+Foxp3- T cells. TCR repertoire analysis indicated very little overlap between Helios+ and Helios- Treg. Thus, Helios+ and Helios- Treg subpopulations are phenotypically and functionally distinct, consistent with thymic and peripheral sites of origin, respectively. Because of their superior suppressive activity and enhanced stability Foxp3+Helios+ Treg represent the optimal Treg population for cellular immunotherapy.

2019-01-24 | GSE117989 | GEO

Helios enhances the preferential differentiation of human fetal CD4+ naïve T cells into regulatory T cells.

Project description:Helios enhances the preferential differentiation of human fetal CD4+ naïve T cells into regulatory T cells.

| PRJNA433827 | ENA

Helios enhances the preferential differentiation of human fetal CD4+ naïve T cells into regulatory T cells. [Epigenetics]

Project description:Helios enhances the preferential differentiation of human fetal CD4+ naïve T cells into regulatory T cells. [Epigenetics]

| PRJNA433824 | ENA

Helios enhances the preferential differentiation of human fetal CD4+ naïve T cells into regulatory T cells. [Epigenetics]

Project description:Human fetal naïve T cells preferentially differentiate into CD25hiFOXP3hi regulatory T (Treg) cells upon T cell receptor (TCR) stimulation, which contribute to the generation of immunotolerance in the developing human fetus. We utilized ATACseq and H3K27ac ChIPseq to characterize the human fetal naive T cell epigenome relative to that of adult naive T cells and Treg cells. Fetal naive T cells share a partial Treg epigenome with increased chromatin accessibility and H3K27ac enrichment at a subset of Treg-specific enhancers.

2019-11-22 | GSE110468 | GEO

Helios enhances the preferential differentiation of human fetal CD4+ naïve T cells into regulatory T cells. [RNA-Seq - ex vivo]

Project description:RNA sequencing was used to compare the transcriptome of ex vivo isolated adult and fetal naïve and regulatory T (Treg) cells. A Treg-specific transcriptome was defined by genes upregulated and downregulated preferentially in adult and fetal Treg cells relative to adult naive T cells. Fetal naive T cells show an intermediate expression of genes in the Treg-specific transcriptome.

2019-11-22 | GSE110469 | GEO

Stable inhibitory activity of regulatory T cells requires the transcription factor Helios

Project description:The maintenance of immune homeostasis requires regulatory T cells (Tregs). Given their intrinsic self-reactivity, Tregs must stably maintain a suppressive phenotype to avoid autoimmunity. We report that impaired expression of the transcription factor (TF) Helios by FoxP3+ CD4 and Qa-1-restricted CD8 Tregs results in defective regulatory activity and autoimmunity in mice. Helios-deficient Treg develop an unstable phenotype during inflammatory responses characterized by reduced FoxP3 expression and increased effector cytokine expression secondary to diminished activation of the STAT5 pathway. CD8 Treg also require Helios-dependent STAT5 activation for survival and to prevent terminal T cell differentiation. Definition of Helios as a key transcription factor that stabilizes regulatory T-cells in the face of inflammatory responses provides a genetic explanation for a core property of regulatory T-cells. We used microarrays to detail the global programs of gene expression by CD8 Treg (CD44+CD122+Ly49+) and conventional memory type of CD8 cells (CD44+CD122+Ly49-).

2015-09-15 | E-GEOD-73015 | biostudies-arrayexpress

Helios enhances the preferential differentiation of human fetal CD4+ naïve T cells into regulatory T cells. [RNA-Seq - ex vivo]

Project description:Helios enhances the preferential differentiation of human fetal CD4+ naïve T cells into regulatory T cells. [RNA-Seq - ex vivo]

| PRJNA433825 | ENA

Helios expression defines two distinct populations of Foxp3+ Treg cells

Project description:Helios expression defines two distinct populations of Foxp3+ Treg cells

| PRJNA483941 | ENA

Stable inhibitory activity of regulatory T cells requires the transcription factor Helios

2015-09-15 | GSE73015 | GEO