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RNA sequencing of CD4+ and CD8+ subsets of human engineered regulatory T cell lines expressing FOXP3, FOXP+Helios-FL, FOXP3+Helios-Δ3b

ABSTRACT: RNA sequencing of CD4+ and CD8+ subsets of human engineered regulatory T cell lines expressing FOXP3, FOXP+Helios-FL, FOXP3+Helios-Δ3b

PROVIDER: PRJNA558955 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR9910610_1.fastq.gz	Fastqsanger.gz
	SRR9910610_2.fastq.gz	Fastqsanger.gz
	SRR9910620_1.fastq.gz	Fastqsanger.gz
	SRR9910620_2.fastq.gz	Fastqsanger.gz
	SRR9910611_1.fastq.gz	Fastqsanger.gz

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RNA sequencing of CD4+ and CD8+ subsets of human engineered regulatory T cell lines expressing FOXP3, FOXP+Helios-FL, FOXP3+Helios-Δ3b

Project description:We report RNA sequencing data for three human engineered regulatory T cell lines expressing FOXP3, FOXP+Helios-FL, FOXP3+Helios-Δ3b. From total RNA from 3 biological replicates from each cell line, we generated RNA Sequencing data that compared gene expression between CD4+ and CD8+ cells for each cell line. RNA Sequencing demonstrated that the addition of full-length Helios changed gene expression in cellular pathways and the Treg signature compared to FOXP3 alone or the other major Helios isoform.

2020-04-20 | GSE135452 | 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

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-).

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Helios expression defines two distinct populations of Foxp3+ Treg cells

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

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Immune Gene Expression Profile of Conventional and Regulatory T cells

Project description:Understanding human regulatory T cells (Tregs) heterogeneity may identify markers of disease pathogenesis and facilitate the development of optimized cellular therapeutics. To better elucidate human Treg subsets, we conducted direct transcriptional profiling of CD4+FOXP3+Helios+ thymic-derived Treg (tTreg) and CD4+FOXP3+Helios- peripherally-induced Treg (pTreg), followed by comparison to CD4+FOXP3-Helios- T conventional (Tconv) cells. This analysis revealed that the coinhibitory receptor T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) was highly expressed on tTreg. In this study CD4 T cells were stained for the Treg-associated transcription factors FOXP3 and Helios, and subsequently FACS sorted to yield three populations: tTreg (CD4+FOXP3+Helios+), pTreg (CD4+FOXP3+Helios–) and the reference population Tconv (CD4+FOXP3–Helios–). A direct transcriptional profile was obtained from the recovered RNA from the populations defined as tTreg, pTreg, and Tconv.

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Food protein-induced activation and death of CD4+ Helios+ Foxp3- T cells is required for IL-10 production and intestinal homeostasis

Project description:The impact of dietary proteins on homeostasis and immune function of the intestine is poorly understood. We here show that physiological uptake of dietary proteins induced an activated, CD4+CD44+Helios+ T cell population, predominantly in Peyer's patches (PP). These cells are distinct from Foxp3+regulatory T cells and microbiota-independent. Dietary protein-reactive T lymphocytes remained innocuous due to an equilibrium between activation and apoptosis. Macrophage mediated uptake of apoptotic T cells from the PP but not from other tissues resulted in strong IL-10 expression. In contrast, replacement of dietary proteins by amino acids resulted in low numbers of activated and apoptotic CD4+CD44+Helios+ T cells together with reduced amounts of IL-10 and downregulation of genes involved in intestinal integrity such as trefoil factors and gastrokines. The impaired intestinal barrier function of these animals was restored after switching to conventional diet, demonstrating the essential role of food proteins for induction of epithelial repair mechanisms and immunological homeostasis. Microarray experiments were performed as dual-color hybridizations on Agilent-014868 Whole Mouse Genome 4x44K catalog arrays. To compensate for dye-specific effects, a dye-reversal color-swap was applied.

2016-07-01 | E-GEOD-66938 | biostudies-arrayexpress

Effect of NIK overexpression on Foxp3+CD4+ and Foxp3-CD4+ T cell subsets

Project description:Effect of NIK overexpression on Foxp3+CD4+ and Foxp3-CD4+ T cell subsets

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