Browse
Submit Data
Databases
API
Help

Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

55 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

IFNγ signaling endows DCs with the capacity to control type I inflammation during parasitic infection through promoting T-bet+ regulatory T cells

ABSTRACT: Transcriptome analysis of IFNγ-insensitive DCs IFNγ signaling drives dendritic cells (DCs) to promote type I T cell (Th1) immunity. Here, we show that activation of DCs by IFNγ is equally crucial for the differentiation of a population of T-bet+ regulatory T (Treg) cells specialized to inhibit Th1 immune responses. Conditional deletion of IFNγ receptor in DCs but not in Treg cells resulted in a severe defect in this specific Treg cell subset, leading to exacerbated immune pathology during parasitic infections. Mechanistically, IFNγ-unresponsive DCs failed to produce sufficient amount of IL-27, a cytokine required for optimal T-bet induction in Treg cells. Thus, IFNγ signalling endows DCs with the ability to efficiently control a specific type of T cell immunity through promoting a corresponding Treg cell population. We analyzed saliva from 3 WT DC samples and 3 IFNγR2 KO DC samples isolated from unmanipulated mice. In addition, we analyzed saliva from 3 WT DC samples and 3 IFNγR2 KO DC samples isolated from mixed BM chimeras (WT + IFNgR2KO) day 8 T. gondii infected.

ORGANISM(S): Mus musculus

SUBMITTER: Li-Fan Lu

PROVIDER: E-GEOD-64594 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

IFNγ signaling endows DCs with the capacity to control type I inflammation during parasitic infection through promoting T-bet+ regulatory T cells

Project description:Transcriptome analysis of IFNγ-insensitive DCs IFNγ signaling drives dendritic cells (DCs) to promote type I T cell (Th1) immunity. Here, we show that activation of DCs by IFNγ is equally crucial for the differentiation of a population of T-bet+ regulatory T (Treg) cells specialized to inhibit Th1 immune responses. Conditional deletion of IFNγ receptor in DCs but not in Treg cells resulted in a severe defect in this specific Treg cell subset, leading to exacerbated immune pathology during parasitic infections. Mechanistically, IFNγ-unresponsive DCs failed to produce sufficient amount of IL-27, a cytokine required for optimal T-bet induction in Treg cells. Thus, IFNγ signalling endows DCs with the ability to efficiently control a specific type of T cell immunity through promoting a corresponding Treg cell population.

2015-01-01 | GSE64594 | GEO

Functions of BET proteins in GATA1-mediated transcription [expression array]

Project description:Role of bromodomain and extra-terminal motif (BET) proteins in GATA1-null erythrolbasts (G1E) and in differentiation induced by activation of conditional GATA1 tested by addition of BET inhibitor JQ1 (250nM) Array protocols were conducted as described in the Ambion WT Expression Manual and the Affymetrix GeneChip Expression Analysis Technical Manual by the University of Pennsylvania Molecular Profiling Core. Two-factor design (+/- JQ1, +/- GATA1). External RNA spike-in controls (ERCC controls, Ambion) added to each sample in proportion to cell number at the time of RNA harvest.

2015-02-23 | E-GEOD-62709 | biostudies-arrayexpress

IL-12 From Endogenous cDC1, and Not Vaccine DC, Is Required for Th1 Induction

Project description:In this study, we generated a chimeric situation by injection of different gene-modified BM-DCs into different strains of gene-modified recipient mice. This allowed us to identify the separate functional contributions of injected versus endogenous DCs for Th1 polarization. We identified the cellular source of IL-12p70 production after subcutaneous BM-DC vaccination as endogenous migratory XCR1+ bystander DCs in the skin draining lymph nodes. DC-DC and DCT cell interaction studies revealed a time course of Th0 priming by injected BM-DCs, followed by interactions of BM-DC with the IL-12+ XCR1+ bystander DCs, and finally IL-12+ XCR1+ bystander DC interactions for Th1 induction. Transcriptional profiling of the bystander DCs underscores their Th1 polarization potential. Together, this study shows that DC-vaccination requires the bystander activation of endogenous DCs for Th1 priming. Our data also challenge the general concept of Th1 priming by a single DC providing all signals 1, 2 and 3 to T cells for Th1 polarization.

2020-06-02 | GSE124677 | GEO

Expression data in splenic DC subsets in wild type and Xbp1 deficient mice

Project description:Xbp1 is a major transcription factor in the unfolded protein response. To uncover its function in DCs we generated a conditional KO for Xbp1 in dendritic cells. We here compare the expression of mRNAs in two different splenic DC subpopulations, CD8a and CD11b DCs in both WT and KO mice. Reference: Inositol-requiring enzyme 1-alpha regulates CD8a dendritic cell function via regulated mRNA decay. Osorio et al, Nature Immunology (2014) Primary DC subsets were isolated and sorted from spleens from 3 different WT or CD11c-cre Xbp-1fl/fl mice. RNA was isolated, converted to cDNA and then hybridised on Affymetrix GeneChip Mouse Gene 1.0 ST Arrays (GPL6246).

2014-01-01 | E-GEOD-52857 | biostudies-arrayexpress

CXCR3+ Treg cells suppress Th1-immune responses through expression of the co-inhibitory receptors CD85k and Lag-3

Project description:CD4+Foxp3+ Treg cells are essential for maintaining self-tolerance and preventing excessive immune responses. In the context of Th1 immune responses, co-expression of the Th1 transcription factor T-bet with Foxp3 is essential for Treg cells to control Th1 responses. T-bet-dependent expression of CXCR3 directs Tregs to the site of inflammation, however, the suppressive mediators enabling effective control of Th1 responses at this site are unknown. In this study, we determined the signature of CXCR3+ Treg cells arising in Th1 settings and defined universal features of Treg cells in this context using multiple Th1-dominated models. Our analysis defined a set of Th1-specific co-inhibitory receptors that are specifically expressed in Treg cells during Th1 immune responses. Among these, we identified the novel co-inhibitory receptor CD85k as a functional mediator of the enhanced suppression of Th1 effector cells by CXCR3+ Treg cells.

2018-06-30 | E-MTAB-6156 | biostudies-arrayexpress

Enterobacter ludwigii protects DSS-induced colitis through choline-mediated immune tolerance

Project description:Commensal intestinal bacteria play key roles in regulating cells mediating immune tolerance; however, bacterial strains and related metabolites directly involved in this regulation are largely unknown. Here, using a mouse model of dextran sulfate sodium (DSS)-induced colitis combined with different antibiotic treatment, Enterobacter ludwigii, abundant in microbiota of mice treated with metronidazole, was screened out to have prophylactic and therapeutic effects on DSS-induced colitis with or without the presence of complex intestinal bacteria. E. ludwigii was demonstrated to induce CD103+DC and Treg-mediated immune tolerance for colitis remission using in vitro and in vivo experiments. Moreover, choline, one of E. ludwigii metabolites, was identified to increase DCs’ immune tolerance to promote Treg differentiation. E. ludwigii was found to induce DCs’ immune tolerance ability for Treg differentiation through choline and α7nAChR-mediated RA and TGF-β upregulation, resulting in protecting mice against DSS-induced colitis. This study provides potential therapeutic approaches for IBD.

2024-08-05 | MTBLS5585 | MetaboLights

Interferon gamma-induction of TH1-like regulatory T cells controls anti-viral responses

Project description:Regulatory T cells (Tregs) are an immunosuppressive population that are required to maintain peripheral tolerance and prevent tissue damage during immunopathology, via anti-inflammatory cytokines, inhibitor receptors and metabolic disruption. We report that Tregs acquire an effector-like state, yet remain stable and functional, when exposed to IFNγ during chronic infection with lymphocytic choriomeningitis (LCMV) and Influenza A virus (IAV). Mechanistically, Treg-restricted-deletion of the IFNγ receptor 1 (IFNGR1), but not the IL12 receptor, prevented TH1-like polarization (decreased expression of T-bet, CXCR3 and IFNγ) and promoted TH2-like polarization (increased expression of GATA-3, CCR4 and IL4). TH1-like Tregs limited CD8+ T cell effector function, proliferation and memory formation during chronic and acute infection. These findings provide fundamental insights into how Tregs sense inflammatory cues from the environment (IFNγ) during viral infection to provide immune guidance to the effector T cell response, to prevent prolonged immunoinflammatory responses and shape the quality of the memory response.

2023-01-23 | GSE223210 | GEO

Comparison of gene expression in AhR WT (+/+) and AhR KO (-/-) primary mouse keratinocytes

Project description:The AhR is a ligand activated transcription factor that may be important in normal skin physiology. We compared gene expression profiles between AhR Wt and AhR KO primary mouse keratinocyte cultures. We identified 391 genes that were differentially expressed with a 1.5 fold cutoff and p<.05, and identified the AhR as an important regulator of genes involved in normal epidermal differentiation. AhR Wt primary keratinocyte cultures (n=4) were compared with AhR KO primary keratinocyte cultures (n=3)

2015-07-01 | E-GEOD-62490 | biostudies-arrayexpress

Gene expression profile analysis of Regulatory T cell-conditioned dendritic cells to elucidate the mechanisms underpinning dendritic cell suppression in graft versus host disease (GvHD)

Project description:Gene expression profiling of Treg-conditioned dendritic cells (DCs) compared to LPS-matured DCs and immature DCs. The hypothesis tested in the present study was that Treg conditioning alters the gene expression profile of DCs to result in that of a semi-mature phenotype. The results provide important information on how Tregs modulate DC function.

2017-03-01 | GSE72893 | GEO

Molecular signatures of maturing dendritic cells: implications for testing the quality dendritic cell therapies

Project description:Abstract Background: Dendritic cells (DCs) are often produced by granulocyte-macrophage colony-stimulating factor (GMCSF) and interleukin-4 (IL-4) stimulation of monocytes. To improve the effectiveness of DC adoptive immune cancer therapy, many different agents have been used to mature DCs. We analyzed the kinetics of DC maturation by lipopolysaccharide (LPS) and interferon-g (IFN-g) induction in order to characterize the usefulness of mature DCs (mDCs) for immune therapy and to identify biomarkers for assessing the quality of mDCs. Methods: Peripheral blood mononuclear cells were collected from 6 healthy subjects by apheresis, monocytes were isolated by elutriation, and immature DCs (iDCs) were produced by 3 days of culture with GM-CSF and IL-4. The iDCs were sampled after 4, 8 and 24 hours in culture with LPS and IFN-g and were then assessed by flow cytometry, ELISA, and global gene and microRNA (miRNA) expression analysis. Results: After 24 hours of LPS and IFN-g stimulation, DC surface expression of CD80, CD83, CD86, and HLA Class II antigens were up-regulated. Th1 attractant genes such as CXCL9, CXCL10, CXCL11 and CCL5 were up-regulated during maturation but not Treg attractants such as CCL22 and CXCL12. The expression of classical mDC biomarker genes CD83, CCR7, CCL5, CCL8, SOD2, MT2A, OASL, GBP1 and HES4 were up-regulated throughout maturation while MTIB, MTIE, MTIG, MTIH, GADD45A and LAMP3 were only up-regulated late in maturation. The expression of miR-155 was up-regulated 8-fold in mDCs. Conclusion: DCs, matured with LPS and IFN-g, were characterized by increased levels of Th1 attractants as opposed to Treg attractants and may be particularly effective for adoptive immune cancer therapy.

2018-03-08 | GSE111581 | 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