Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A function for interleukin 2 in Foxp3-expressing regulatory T cells

ABSTRACT: Regulatory T cells (Treg cells) expressing the forkhead family transcription factor Foxp3 are critical mediators of dominant immune tolerance to self. Most Treg cells constitutively express the high-affinity interleukin 2 (IL-2) receptor alpha-chain (CD25); however, the precise function of IL-2 in Treg cell biology has remained controversial. To directly assess the effect of IL-2 signaling on Treg cell development and function, we analyzed mice containing the Foxp3gfp knock-in allele that were genetically deficient in either IL-2 (Il2-/-) or CD25 (Il2ra-/-). We found that IL-2 signaling was dispensable for the induction of Foxp3 expression in thymocytes from these mice, which indicated that IL-2 signaling does not have a nonredundant function in the development of Treg cells. Unexpectedly, Il2-/- and Il2ra-/- Treg cells were fully able to suppress T cell proliferation in vitro. In contrast, Foxp3 was not expressed in thymocytes or peripheral T cells from Il2rg-/- mice. Gene expression analysis showed that IL-2 signaling was required for maintenance of the expression of genes involved in the regulation of cell growth and metabolism. Thus, IL-2 signaling seems to be critically required for maintaining the homeostasis and competitive fitness of Treg cells in vivo. Keywords: cell type comparison

ORGANISM(S): Mus musculus

PROVIDER: GSE4179 | GEO | 2006/02/09

SECONDARY ACCESSION(S): PRJNA94983

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Transcription profiling of mouse Foxp3-expressing regulatory T cells

Project description:Regulatory T cells (Treg cells) expressing the forkhead family transcription factor Foxp3 are critical mediators of dominant immune tolerance to self. Most Treg cells constitutively express the high-affinity interleukin 2 (IL-2) receptor alpha-chain (CD25); however, the precise function of IL-2 in Treg cell biology has remained controversial. To directly assess the effect of IL-2 signaling on Treg cell development and function, we analyzed mice containing the Foxp3gfp knock-in allele that were genetically deficient in either IL-2 (Il2-/-) or CD25 (Il2ra-/-). We found that IL-2 signaling was dispensable for the induction of Foxp3 expression in thymocytes from these mice, which indicated that IL-2 signaling does not have a nonredundant function in the development of Treg cells. Unexpectedly, Il2-/- and Il2ra-/- Treg cells were fully able to suppress T cell proliferation in vitro. In contrast, Foxp3 was not expressed in thymocytes or peripheral T cells from Il2rg-/- mice. Gene expression analysis showed that IL-2 signaling was required for maintenance of the expression of genes involved in the regulation of cell growth and metabolism. Thus, IL-2 signaling seems to be critically required for maintaining the homeostasis and competitive fitness of Treg cells in vivo. Experiment Overall Design: We isolated Foxp3+ CD4+ T cells from Il2-/- mice treated with PBS or recombinant IL-2 for gene expression analysis using whole-genome oligonucleotide microarrays. To identify gene expression changes resulting from IL-2 deficiency and subsequent IL-2 stimulation in Treg cells, we directly compared expression profiles with each other and with expression profiles of Foxp3+ CD4+ T cells isolated from wild-type mice.

2008-06-13 | E-GEOD-4179 | biostudies-arrayexpress

Mus musculus

Project description:Gene expression profiles of CD4SP Foxp3GFP-CD25+ Treg precursors and Foxp3GFP-CD25- thymocytes

| PRJNA178934 | ENA

Single-cell RNA-seq uncovers unique gene expression profiles in the spleen of hypoxic mice

Project description:The stability of FOXP3 expression in Tregs influences the balance between tolerance and autoimmunity. Treg cell development and function are regulated by IL-2, which binds to IL-2Rα (also called CD25). Decreased expression of CD25 (Il2ra gene) characterizes Tregs that lose FOXP3 expression (exTregs) and undergo transdifferentiation into TH17 cells. This has been established under arthritic conditions but whether this Treg transdifferenciation into exTregs occur following hypoxia exposure, it is unknown. Therefore, single-cell RNA-seq (10x Genomics) was performed using a 10X Genomics Chromium system to test the hypothesis that hypothesis that chronic hypoxia initiates Treg transcriptional reprogramming.

2024-01-16 | GSE219259 | GEO

scRNAseq transcriptome analysis of developing regulatory T cells and precursors in the thymus

Project description:We analyzed the individual transcriptomes of thymic Treg cells (CD4+Foxp3+), their immediate precursors (CD25+CD4+Foxp3-) and mature CD4 single positive thymocytes (CD4+Foxp3-CD25-CD62L+CD24-).

2019-08-19 | GSE134902 | GEO

miR-182 and miR-10a are Key Regulators of Treg specialisation and stability during Th2 and Th1-associated Inflammation

Project description:A variety of CD4+Foxp3+ Treg cell types have been described previously, indicating molecular heterogeneity within the Foxp3+ pool of CD4+ T cells. However, the factors that shape the transcriptomic identities of different Foxp3+ Treg cells are poorly understood. To identify the molecular pathways involved, we isolated CD4+Foxp3gfp+ cells from Th1-rich or Th2-rich environments following chronic Leishmania major or Schistosoma mansoni infection, respectively. Whole genome expression profiling and next generation small RNA sequencing revealed significantly different mRNA and miRNA profiles. In-silico analyses identified miR-10a and miR-182 as âregulatory miRNA hubsâ in CD4+Foxp3+ cells in Th1 and Th2-environments, respectively. Using in vitro and in vivo systems we identified that IL-12/IFNg down-regulated miR-10a and its putative transcription factor, Creb. Importantly, we demonstrated that miR-10a controls a suite of genes that regulate IFNg production in Th1-Treg cells. Also, Treg cells treated with IL-4 increased miR-182 and its putative transcription factor, cMaf. Up-regulation of miR-182 mitigated IL-2 secretion, in part through repression of IL2-promoting genes, including Bach2 and Cd2ap. This study indicates that CD4+Foxp3+ cells are influenced by their environment, and that Th1 or Th2 environments promote distinct miRNA pathways, preserving Treg stability and suppressor function. mouse infection vs. naÃ¯ve

2016-04-07 | E-GEOD-45976 | biostudies-arrayexpress

Tracking regulatory T cell development in the thymus using scRNA-Seq/TCR-Seq

Project description:Recent studies have demonstrated that mature regulatory T cells ( Tregs) develop in the thymus via two pathways involving distinct Treg progenitors (TregP) - CD25+FOXP3- (CD25+ TregP) and CD25-FOXP3lo (FOXP3lo TregP) Treg progenitors. To examine this process in more detail we carried out single-cell RNA-Seq and TCR-Seq on sorted CD4+CD8+ double-positive (DP) thymocytes, CD4+ Ssingle -positive (CD4SP)P thymocytes, CD25+ TregP, FOXP3lo TregP, mature CD25+FOXP3+ Tregs and recirculating/long-term resident Tregs (RT-Tregs). Sorted populations were individually hashtagged and then combined into one scRNA-Seq/TCR-Seq library before sequencing and subsequent analysis. We found that both CD25+ TregP and FOXP3lo TregP arise via an initial agonist activated state that gives rise to a second transitional stage before differentiating into mature Tregs. Using both scRNA-Seq and bulk RNA-Seq on sorted thymocyte subsets we demonstrate that CD25+Foxp3- TregP are significantly enriched for Il2 production, suggesting that they are the major source of IL-2 needed to convert TregP into mature Tregs. Using TCR-Seq we found that several TCRs were clearly biased in favor of the conventional or Treg lineages, but that a large fraction of TCRs were found in both these lineages. Finally, we found that recirculating/resident Tregs in the thymus are not monomorphic, but are composed of multiple distinct subsets and that these RT-Tregs express the most diverse TCR repertoire of all CD4SP thymcocytes. Thus, our studies define multiple stages of Treg differentiation within the thymus, and serve as a resource for future studies on CD4+ thymocyte development and Treg differentiation.

2022-06-30 | GSE202871 | GEO

miR-182 and miR-10a are Key Regulators of Treg specialisation and stability during Th2 and Th1-associated Inflammation

Project description:A variety of CD4+Foxp3+ Treg cell types have been described previously, indicating molecular heterogeneity within the Foxp3+ pool of CD4+ T cells. However, the factors that shape the transcriptomic identities of different Foxp3+ Treg cells are poorly understood. To identify the molecular pathways involved, we isolated CD4+Foxp3gfp+ cells from Th1-rich or Th2-rich environments following chronic Leishmania major or Schistosoma mansoni infection, respectively. Whole genome expression profiling and next generation small RNA sequencing revealed significantly different mRNA and miRNA profiles. In-silico analyses identified miR-10a and miR-182 as ‘regulatory miRNA hubs’ in CD4+Foxp3+ cells in Th1 and Th2-environments, respectively. Using in vitro and in vivo systems we identified that IL-12/IFNg down-regulated miR-10a and its putative transcription factor, Creb. Importantly, we demonstrated that miR-10a controls a suite of genes that regulate IFNg production in Th1-Treg cells. Also, Treg cells treated with IL-4 increased miR-182 and its putative transcription factor, cMaf. Up-regulation of miR-182 mitigated IL-2 secretion, in part through repression of IL2-promoting genes, including Bach2 and Cd2ap. This study indicates that CD4+Foxp3+ cells are influenced by their environment, and that Th1 or Th2 environments promote distinct miRNA pathways, preserving Treg stability and suppressor function.

2016-04-07 | GSE45976 | GEO

Expression data of PRDM1α or empty vector-transduced NK92 or KHYG1 cell lines

Project description:CD25 (IL2RA) is a subunit of IL2 receptor complex, which determines the sensitivity of the receptor to IL2. Here, we investigated whether PRDM1, a transcriptional repressor implicated as a tumor suppressor in NK cell malignancies, directly represses CD25 (IL2RA). Using ChIP-seq, we identified a direct binding site of PRDM1 within 1st intron of CD25 (IL2RA) in activated primary human NK cells. We used DNA microarrays on two PRDM1α transduced NK cell lines (i.e. NK92 and KHYG1) to address whether PRDM1 transcriptionally represses CD25.

2021-05-05 | GSE157206 | GEO

RNA-seq and ChIP-seq to study how transcription factor Foxp1 regulates Foxp3 binding to chromatin and coordinates regulatory T cell function

Project description:Regulatory T (Treg) cells, whose differentiation and function are controlled by transcription factor Foxp3, express high amounts of a closely related family member Foxp1, which is also expressed in quiescent naive T cells. Here we explored Foxp1 function in Treg cells. We found that a large number of Foxp3-bound genomic sites in Treg cells were occupied by Foxp1 in both Treg and conventional T cells. In Treg cells, Foxp1 markedly increased Foxp3 binding to these sites, which were enriched for canonic forkhead and Ets binding motifs. Foxp1 deficiency in Treg cells resulted in their impaired function and competitive fitness associated with markedly reduced CD25 expression and interleukin-2 (IL-2) responsiveness, diminished CTLA-4 and increased SATB1 expression. The characteristic patterns of CD25, Foxp3, and CTLA-4 expression in Treg cells were rescued, at least in part, upon strong IL-2 signaling. Our studies suggest that in addition to the Foxp1-mediated regulation of quiescence that is common to Treg and conventional T cells, Foxp1 has an essential non-redundant function in Treg cells by enforcing Foxp3-mediated regulation of gene expression and enabling efficient IL-2 signaling in these cells.

2019-01-18 | GSE121279 | GEO

Loss of Foxp3-driven epigenetic modification leads to regulatory T cell insufficiency

Project description:Regulatory T cells (Tregs) are responsible for limiting autoimmunity and chronic inflammation. Foxp3 is a transcription factor that acts as a master regulator of Treg development and function. A serendipitous observation led to the realization that a well-characterized Foxp3gfp reporter mouse, which expresses an N-terminal GFP-Foxp3 fusion protein, is a hypomorph that causes profoundly accelerated autoimmune diabetes on a NOD background. Although natural Treg development and in vitro function is not significantly altered in Foxp3gfp NOD and C57BL/6 mice, Treg fitness function in inflammatory environments is perturbed and TGF?-induced Treg development reduced. Foxp3gfpis unable to interact with the histone acetyltransferase Tip60, the histone deacetylase HDAC7, and the Ikaros family zinc finger 4, Eos, which leads to reduced Foxp3 acetylation and enhanced K48-linked polyubiquitylation. Collectively this leads to an altered transcriptional landscape and reduced Foxp3-mediated gene repression, notably at the hallmark IL-2 promoter. Loss of controlled Foxp3-driven epigenetic modification leads to Treg insufficiency that causes autoimmunity in prone environments. 16 samples overall split between 2 genotypes (wild type and Foxp3 knock in) and two cell types (Tregs and Tconv)

2012-12-07 | E-GEOD-35164 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data