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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: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE131589 | GEO | 2019/11/22

REPOSITORIES: GEO

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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.

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

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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.

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2022-11-28 | PXD038302 | Pride

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

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

| PRJNA544098 | ENA

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