Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

FoxP3-mediated blockage of ryanodine receptor 2 is the molecular basis for the contact-based suppression by regulatory T cells

ABSTRACT: FoxP3-mediated blockage of ryanodine receptor 2 is the molecular basis for the contact-based suppression by regulatory T cells

PROVIDER: PRJNA993577 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR25232070_1.fastq.gz	Fastqsanger.gz
	SRR25232070_2.fastq.gz	Fastqsanger.gz
	SRR25232071_1.fastq.gz	Fastqsanger.gz
	SRR25232071_2.fastq.gz	Fastqsanger.gz
	SRR25232072_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 32

Similar Datasets

FoxP3-mediated blockage of ryanodine receptor 2 is the molecular basis for the contact-based suppression by regulatory T cells

Project description:The suppression mechanism of regulatory T cells (Tregs) is an intensely investigated topic. As our focus has shifted towards a model centered on indirect inhibition of dendritic cells, a universally applicable effector mechanism controlled by the transcription factor forkhead box P3 (FoxP3) expression has not been found. Here, we report that FoxP3 blocks the transcription of ER Ca2+-release channel ryanodine receptor 2 (RyR2). Reduced RyR2 shuts down basal Ca2+ oscillation in Tregs, which reduces m-Calpain activities that is needed for T cells to disengage from DCs, suggesting a persistent blockage of DC antigen presentation. RyR2 deficiency renders the CD4+ T cell pool to become immune suppressive, and behave in the same manner as FoxP3+ Tregs in viral infection, asthma, hypersensitivity, colitis and tumor development. In the absence of FoxP3, RyR2-deficient CD4+ T cells (CKO) rescue the systemic autoimmunity associated with Scurfy mice. Therefore, FoxP3-mediated Ca2+ signaling inhibition may be a central effector mechanism of Treg immune suppression.

2023-12-20 | GSE237032 | GEO

Foxp3-mediated blockage of ryanodine receptor 2 underlies contact-based suppression by regulatory T cells.

Project description:The suppression mechanism of Tregs remains an intensely investigated topic. As our focus has shifted toward a model centered on indirect inhibition of DCs, a universally applicable effector mechanism controlled by the transcription factor forkhead box P3 (Foxp3) expression has not been found. Here, we report that Foxp3 blocked the transcription of ER Ca2+-release channel ryanodine receptor 2 (RyR2). Reduced RyR2 shut down basal Ca2+ oscillation in Tregs, which reduced m-calpain activities that are needed for T cells to disengage from DCs, suggesting a persistent blockage of DC antigen presentation. RyR2 deficiency rendered the CD4+ T cell pool immune suppressive and caused it to behave in the same manner as Foxp3+ Tregs in viral infection, asthma, hypersensitivity, colitis, and tumor development. In the absence of Foxp3, Ryr2-deficient CD4+ T cells rescued the systemic autoimmunity associated with scurfy mice. Therefore, Foxp3-mediated Ca2+ signaling inhibition may be a central effector mechanism of Treg immune suppression.

| S-EPMC10721146 | biostudies-literature

Identify proteins at Foxp3 bound cis-regulatory elements in situ

Project description:We hypothesize that nuclear factors co-occupying the genetic elements with regulatory T (Treg) cell lineage–specifying factor Foxp3 play critical roles in transcriptional regulation of Treg immune suppression function, thus, offering a unique approach to investigate the factors and their mechanisms controlling Treg-mediated immune tolerance involved in self-tolerance and antitumor immunity. We seek to identify the proteins occupying Foxp3 targets in the resting state or after cells receiving stimulation. To this end, we projected the spatial information (PSI) of Foxp3, Histone H3, or Stat5 onto their adjacent proteins with peroxidase–catalyzed biotin-phenoxyl radicals and identify these biotinylated proteins with tandem mass tag (TMT)–based quantitative mass spectrometry (MS).

2024-06-08 | PXD019050 | Pride

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

Project description:We previously found that NF-kB inducing kinase (NIK) overexpression in T cells via CD4 promoter driven transgene induction caused lethal autoimmunity in mice. Autoimmunity was associated with increased conventional T cell effector function and decreased regulatory T cell (Foxp3+CD4+) suppression. The goal in this study was to elucidate global transcriptional changes in Foxp3+CD4+ and Foxp3-CD4+ T cells intrinsically caused by chronic NIK overexpression in these cell types.

2016-04-29 | GSE80755 | GEO

Foxp3 positive and negative cell comparison

Project description:Regulatory T cells have been shown to adopt a catabolic metabolic programme with increased capacity for fatty acid oxidation fuelled oxidative phosphorylation (OXPHOS). The role of Foxp3 in this metabolic shift is poorly understood. Here we show that Foxp3 was sufficient to induce a significant increase in the spare respiratory capacity of the cell, the extra OXPHOS capacity available to a cell to increased demands on energy in response to work. Foxp3-expressing cells were enhanced in their ability to utilise palmitate for respiration and in addition the activity of electron transport complexes I, II and IV were enhanced following Foxp3 expression. ATP was secreted by both T effector and regulatory T cells and was reduced by mitochondrial respiration inhibitors. Thus Foxp3 imparts a selective advantage in ATP generation capacity to the cell and may exploit this as a source of adenosine for functional immunomodulation. In order to explore possible mechanisms for these differences in metabolism we conducted a comparative quantitative proteomics study to compare the contribution of TGFβ and the transcription factor Foxp3 to the Treg proteome. We used quantitative mass spectrometry to examine differences between proteomes of nuclear and cytoplasmic Foxp3-containing T cells and Foxp3 positive iTreg and Foxp3 negative activated CD4 T cells in addition to human peripheral blood natural Treg. Gene set enrichment analysis of our proteomic datasets demonstrated that Foxp3 drives a significant up regulation of several members of the mitochondrial electron transport chain.

2017-02-15 | PXD001789 | Pride

Chromatin immunoprecipitation of Foxp3 in mouse T-cell hybridoma cells

Project description:The forkhead transcription factor Foxp3 is essential for the development of CD4+CD25+ regulatory T (Treg) cells and prevention of autoimmunity, but how it controls the Treg gene expression program is not understood. We describe here genome-wide location and expression data that identify Foxp3 target genes and report that many Foxp3 target genes are key modulators of T cell activation and function. Remarkably, the predominant effect of Foxp3 binding is to suppress the activation of target genes upon T cell stimulation. Foxp3 suppression of its targets appears to be crucial for the normal function of Treg cells because overactive variants of some target genes are known to be associated with autoimmune disease.

2007-01-27 | E-TABM-154 | biostudies-arrayexpress

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

2016-04-29 | GSE80756 | GEO

HIC1 interacts with FOXP3 multi protein complex: a novel mechanism to regulate human regulatory T cell differentiation and function

Project description:Recent data have shown that Hypermethylated in cancer 1 (HIC1) is an important contributor to iTreg cell development and function. Using affinity-purification and tandem mass spectrometry we systematically characterized the HIC-1 interactome in human iTreg cells. On the basis of these data, we have shown that HIC1 is a part of FOXP3-RUNX1-CBFβ protein complex that regulates Treg signature genes and is indispensable for the suppressive function of FOXP3+ regulatory T cells. SRM was used to validate HIC1 interactors

2023-10-16 | PXD039337 | Pride

AKT regulates de novo induction of Foxp3

Project description:The CD4+Foxp3+ regulatory T cells play an essential role in maintaining tolerance via their suppressive function on conventional T cells. The intracellular signaling pathways that regulate Foxp3 expression are largely unknown. In this study we describe a novel inhibitory role for AKT in regulating de novo induction of Foxp3 both in vivo and in vitro. A constitutively active allele of AKT significantly diminished TGF-â induced Foxp3 induction via a rapamycin-sensitive pathway, establishing a role for the AKT-mTOR axis in Treg cells. Moreover, the observed impairment in Foxp3 induction was paralleled by a selective downmodulation of the imparted Treg transcriptional signature highlighting the importance of the balance of intracellular signals in Treg differentiation . Our results provide a basis for further elucidation of molecular mechanisms that regulate Foxp3 induction and identify AKT as an important negative regulator of this process. Keywords: Cell population comparison

2008-02-15 | GSE7596 | GEO

Transcription profiling of mouse normal tail skin (no intervention), lymphedema tail skin(due to surgical lymphatic vessel blockage), and surgical Sham control tail skin(surgical incision with no lymphatic vessel blockage)

Project description:We did three sets of microarrays with three replicates each for a total of 9 arrays. Each array was run using pooled RNA from three animals. The three conditions were Normal tail skin (no intervention), Lymphedema tail skin(due to surgical lymphatic vessel blockage), and Surgical Sham control tail skin(surgical incision with no lymphatic vessel blockage). 15ug of test and reference (e17.5 mouse whole embryo) RNA was used for labeling.

2006-06-06 | E-SMDB-3634 | 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