Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Retinoic Acid Enhances Foxp3 Induction Indirectly by Relieving Inhibition from CD4(+)CD44(hi) Cells.

ABSTRACT: CD4(+)Foxp3(+) regulatory T (Treg) cells originate primarily from thymic differentiation, but conversion of mature T lymphocytes to Foxp3 positivity can be elicited by several means, including in vitro activation in the presence of TGF-beta. Retinoic acid (RA) increases TGF-beta-induced expression of Foxp3, through unknown molecular mechanisms. We showed here that, rather than enhancing TGF-beta signaling directly in naive CD4(+) T cells, RA negatively regulated an accompanying population of CD4(+) T cells with a CD44(hi) memory and effector phenotype. These memory cells actively inhibited the TGF-beta-induced conversion of naive CD4(+) T cells through the synthesis of a set of cytokines (IL-4, IL-21, IFN-gamma) whose expression was coordinately curtailed by RA. This indirect effect was evident in vivo and required the expression of the RA receptor alpha. Thus, cytokine-producing CD44(hi) cells actively restrain TGF-beta-mediated Foxp3 expression in naive T cells, and this balance can be shifted or fine-tuned by RA.

ORGANISM(S): Mus musculus

PROVIDER: GSE13306 | GEO | 2008/11/16

SECONDARY ACCESSION(S): PRJNA109885

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Retinoic Acid Enhances Foxp3 Induction Indirectly by Relieving Inhibition from CD4(+)CD44(hi) Cells.

Project description:CD4(+)Foxp3(+) regulatory T (Treg) cells originate primarily from thymic differentiation, but conversion of mature T lymphocytes to Foxp3 positivity can be elicited by several means, including in vitro activation in the presence of TGF-beta. Retinoic acid (RA) increases TGF-beta-induced expression of Foxp3, through unknown molecular mechanisms. We showed here that, rather than enhancing TGF-beta signaling directly in naive CD4(+) T cells, RA negatively regulated an accompanying population of CD4(+) T cells with a CD44(hi) memory and effector phenotype. These memory cells actively inhibited the TGF-beta-induced conversion of naive CD4(+) T cells through the synthesis of a set of cytokines (IL-4, IL-21, IFN-gamma) whose expression was coordinately curtailed by RA. This indirect effect was evident in vivo and required the expression of the RA receptor alpha. Thus, cytokine-producing CD44(hi) cells actively restrain TGF-beta-mediated Foxp3 expression in naive T cells, and this balance can be shifted or fine-tuned by RA. All gene expression profiles were obtained from highly purified T cell populations sorted by flow cytometry. To reduce variability, cells from multiple mice were pooled for sorting, and replicates were generated for essentially all groups. RNA from 0.5-3 x 105 cells was amplified, labeled, and hybridized to Affymetrix M430v2 microarrays. Raw data were preprocessed with the RMA algorithm in GenePattern, and averaged expression values were used for analysis.

2008-11-16 | E-GEOD-13306 | biostudies-arrayexpress

in vitro differentiated Th0, Th17, and Tr1 cells

Project description:Gene expression profiling of in vitro differentiated murine Th cell subsets. Flow cytometrically sorted naive Th cells (CD4+ CD44- Foxp3-) were polyclonally stimulated in vitro for 3 days using 4 µg/ml plate-bound antibody to CD3 (145-2C11) and 2 µg/ml soluble antibody to CD28 (PV-1). Th0 cells were cultured in the absence of exogenous cytokines. Th17 cells were differentiated with 50 ng/ml IL-6 plus 0.5 ng/ml TGF-β. Tr-1 cells were differentiated with 100 ng/ml IL-27 plus 0.5 ng/ml TGF-β.

2014-03-20 | GSE56021 | GEO

TGF-beta/Smad3-dependent gene expression analysis in naive CD4 T cells

Project description:Investigation of transcript level modulation in unstimulated and TGF-beta treated (with or without superimposed T-cell receptor and CD28 stimulation) naive CD4 T cells from wild type or Smad3-deficient littermate mice. Smad3 is a critical signaling molecule and transcription factor downstream of TGF-beta and mediates several of the TGF-beta dependent tolerogenic effects in T cells. This study was undertaken to unveil the transcriptionnal program controled by the TGF-b/Smad3 axis. Microarray study using RNA recovered after 6 hours of culture in either serum free media, serum-free media + TGF-beta (2.5ng/ml) or serum-free media + TGF-beta and anti-CD3e and anti-CD28 stimulation (3 conditions). Naive CD4 T cells (TCRb+, CD4+, CD62L+ and CD44-) were sorted from either wild type or Smad3 deficient littermates and submitted to the 3 culture conditions. Three biological replicates were obtained (each from at least 2 different mice). Thus a total of 18 Nimblegen 365K chip were used.

2012-08-31 | E-GEOD-40494 | biostudies-arrayexpress

Furin deficiency efect on T cells

Project description:Analysis of T-cells lacking the proprotein convertase furin. Proprotein convertases promote the proteolytic maturation of proproteins. Furin is induced in activated T-cells. Results provide insight into the function of furin in T-cells. CD4+CD62L+CD44- naive, CD4+CD62L-CD44+ memory and CD4+CD25+FoxP3+ regulatory T cells were isolated from Fur flox/flox and CD4 cre Fur flox/flox mice. Naive T cells were activated via TCR. Total RNA was extracted from all cells and hybridized to Affymetrix microarrays.

2015-08-05 | E-GEOD-67884 | biostudies-arrayexpress

in vitro differentiated Th0, Th17, and Tr1 cells

Project description:Gene expression profiling of in vitro differentiated murine Th cell subsets. Flow cytometrically sorted naive Th cells (CD4+ CD44- Foxp3-) were polyclonally stimulated in vitro for 3 days using 4 Âµg/ml plate-bound antibody to CD3 (145-2C11) and 2 Âµg/ml soluble antibody to CD28 (PV-1). Th0 cells were cultured in the absence of exogenous cytokines. Th17 cells were differentiated with 50 ng/ml IL-6 plus 0.5 ng/ml TGF-Î². Tr-1 cells were differentiated with 100 ng/ml IL-27 plus 0.5 ng/ml TGF-Î². Five biological replicates per Th subset (Th0, Th17, Tr1)

2014-03-20 | E-GEOD-56021 | biostudies-arrayexpress

Transcription profiling of activated CD4+ T cells from A1.RAGnull mice retrovirally transduced with TGF beta or FoxP3

Project description:To assess the effect of TGF beta or FoxP3 retroviral transduction on transcripts expressed by activated CD4 T cells from A1.RAGnull mice.

2007-12-21 | E-MEXP-1157 | biostudies-arrayexpress

CD44 acts as a co-receptor to confer cell type-specific enhancement of signaling and regulatory T cell induction by TGM-1, a helminth parasite mimic of TGF

Project description:Long-lived parasites evade host immunity through highly evolved molecular strategies. The murine intestinal helminth, Heligmosomoides polygyrus, suppresses the host immune system through release of an immunoregulatory TGF-β mimic, TGM-1, which is a divergent member of the CCP (Sushi) protein family. TGM-1 comprises 5 domains, of which domains 1-3 (D1/2/3) bind mammalian TGFβ receptors, acting on T cells to induce Foxp3+ regulatory T cells; however, the roles of domains 4 and 5 (D4-5) remain unknown. We noted that a truncated TGM-1, lacking these domains, showed reduced potency. Combination of D1/2/3 and D4/5 as separate proteins did not restore full potency, suggesting that a physical linkage is required, and that these domains may not deliver an independent signal. Co-precipitation from cells treated with biotinylated D4/5, followed by mass spectrometry, identified the cell surface protein CD44 as a co-receptor for TGM-1. Both full-length and D4/5 bound strongly to a range of primary cells and cell lines, while D1/2/3 binding was only marginally detectable. Ectopic expression of CD44 in non responding cells conferred responsiveness, while specific genetic depletion of CD44 abolished the enhancement effect of D4/5, and ablated the ability of full-length TGM-1 to bind to cell surfaces. Moreover, CD44-deficient T cells showed attenuated induction of Foxp3 by full-length TGM-1, to levels similar to D1/2/3. Hence, a parasite protein known to bind two host cytokine receptor subunits has evolved a third receptor specificity, which serves to raise the avidity and cell type-specific potency of TGF-β signaling in mammalian cells.

2023-10-24 | PXD037799 | Pride

The kinases MEKK2 and MEKK3 regulate Transforming Growth Factor-β-mediated helper T cell differentiation

Project description:Mitogen-activated protein kinases (MAPKs) are key mediators of the T cell receptor (TCR) signals but their roles in T helper (Th) cell differentiation are unclear. Here we showed that the MAPK kinase kinases MEKK2 (encoded by Map3k2) and MEKK3 (encoded by Map3k3),negatively regulated transforming growth factor-beta (TGF-beta)-mediated Th cell differentiation.Map3k2-/-Map3k3Lck-Cre/- mice showed an abnormal accumulation of regulatory T (Treg) and Th17 cells in the periphery, consistent with Map3k2-/-Map3k3Lck-Cre/- naïve CD4+ T cells’ differentiation into Treg and Th17 cells with a higher frequency than wild-type (WT) cells after TGF-beta stimulation in vitro. In addition, Map3k2-/-Map3k3Lck-Cre/- mice developed more severe experimental autoimmune encephalomyelitis. Map3k2-/-Map3k3Lck-Cre/- T cells exhibited impaired phosphorylation of the SMAD2 and SMAD3 proteins at their linker regions, which negatively regulated the TGF-beta responses in T cells. Thus, the crosstalk between TCR-induced MAPK and the TGF-beta signaling pathways is important in regulating Th cell differentiation. CD4+CD62L-CD44+ cells were FACS sorted from C57BL/6 Lck-Cre MEKK2 KO MEKK3F/-(dKO) or C57BL/6 WT mice

2011-02-02 | E-GEOD-26987 | biostudies-arrayexpress

TGF-beta/Smad3-dependent gene expression analysis in naive CD4 T cells

2012-08-31 | GSE40494 | GEO

Neonatal T helper 17 responses are skewed towards an immunoregulatory interleukin-22 phenotype

Project description:We report broad developmental differences in gene expression profiles between neonatal (term) and adult naive CD4 T cells, resulting in non-stereotypic Th17 differentiation responses to TGF-beta.

2020-12-31 | GSE135467 | GEO

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