Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

ChIP Seq of influenza specific primary, memory and secondary CD4+ T cells [InVitro]

ABSTRACT: Immune responses to infection involve a careful balance: too weak a response allows pathogen replication; too strong risks immunopathology. The immunoregulatory cytokine IL-10 is a key factor in this balance, but the impact of IL-10 is context-dependent and current understanding of the factors that regulate IL-10 is incomplete. In this study, we demonstrated that the infection induced cytokine IL-27 promotes IL-10 expression in CD4+ T cells by directing epigenetic changes in H3K4me3, H3K27me3, H3K4me1 and H3K27Ac modifications at the Il10 locus. We showed that primary activation of antigen-specific CD4+ T cells, in the context of murine influenza infection, led to the long-term remodelling of the epigenetic landscape at both the Il10 promoter and a distinct active enhancer element ~ 25 kb upstream of the TSS. Intact IL-27 signalling was an essential requirement for these persistent epigenetic changes in memory CD4+ Tcells. We identified CREB1 as a transcription factor binding the Il10 active enhancer, and we showed that the ability of IL-27 to promote IL-10 expression was dependent on the histone acetyl transferase activity of the CREB1 complex member, p300. Together our data provide mechanistic insight into the action of IL-27 in regulating an immune response. We suggest that infection-induced cytokine signals direct epigenetic changes that moderate cytokine output in response to T cell receptor stimulation, regulating immune activity at sites of infection.

ORGANISM(S): Mus musculus

PROVIDER: GSE135247 | GEO | 2022/12/31

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

ChIP Seq of influenza specific primary, memory and secondary CD4+ T cells [In Vivo]

Project description:Immune responses to infection involve a careful balance: too weak a response allows pathogen replication; too strong risks immunopathology. The immunoregulatory cytokine IL-10 is a key factor in this balance, but the impact of IL-10 is context-dependent and current understanding of the factors that regulate IL-10 is incomplete. In this study, we demonstrated that the infection induced cytokine IL-27 promotes IL-10 expression in CD4+ T cells by directing epigenetic changes in H3K4me3, H3K27me3, H3K4me1 and H3K27Ac modifications at the Il10 locus. We showed that primary activation of antigen-specific CD4+ T cells, in the context of murine influenza infection, led to the long-term remodelling of the epigenetic landscape at both the Il10 promoter and a distinct active enhancer element ~ 25 kb upstream of the TSS. Intact IL-27 signalling was an essential requirement for these persistent epigenetic changes in memory CD4+ Tcells. We identified CREB1 as a transcription factor binding the Il10 active enhancer, and we showed that the ability of IL-27 to promote IL-10 expression was dependent on the histone acetyl transferase activity of the CREB1 complex member, p300. Together our data provide mechanistic insight into the action of IL-27 in regulating an immune response. We suggest that infection-induced cytokine signals direct epigenetic changes that moderate cytokine output in response to T cell receptor stimulation, regulating immune activity at sites of infection.

2022-12-31 | GSE135249 | GEO

Single cell RNA-seq of IL-10-producing CD4 T cells during chronic LCMV infection

Project description:During chronic viral infection, the inflammatory function of CD4 T cells becomes gradually attenuated. Concurrently, Th1 cells progressively acquire the capacity to secrete the cytokine IL-10, a potent suppressor of antiviral T cell responses. To determine the transcriptional changes that underlie this T cell adaption process, we applied a single-cell RNA-sequencing approach and assessed the heterogeneity of IL-10-expressing CD4 T cells during chronic infection. Unexpectedly, our analyses revealed an IL-10-producing population with a robust Tfh-signature. Using IL-10 and IL-21 double-reporter mice, we further demonstrate that IL-10+IL-21+co-producing Tfh cells arise predominantly during chronic but not acute LCMV infection. Importantly, depletion of IL-10+IL-21+co-producing CD4 T cells or deletion of Il10 specifically in Tfh cells resulted in impaired humoral immunity and viral control. Mechanistically, B cell-intrinsic IL-10 signaling was required for sustaining germinal center reactions. Lastly, we demonstrate that IL-27 and type I IFNs differentially regulate the formation of this protective IL-10-producing Tfh subset. Thus, our findings elucidate a critical role for Tfh-derived IL-10 in promoting humoral immunity during persistent viral infection.

2018-10-29 | GSE111026 | GEO

RNA-seq of Tfh IL21+ single producers and Tfh IL21+ IL10+ double producers

2018-10-29 | GSE111025 | GEO

Blimp-1 and c-Maf regulate Il10 and negatively regulate common and unique proinflammatory gene networks in IL-12 plus IL-27-driven T helper-1 cells [ATAC-Seq]

Project description:CD4+ Th1 cells producing IFN-g are required to eradicate intracellular pathogens, however if uncontrolled these cells can mediate immunopathology. The cytokine IL-10 is produced by multiple immune cells including Th1 cells during infection and regulates the immune response to minimise collateral host damage. In this study we aimed to elucidate the transcriptional network of genes controlling the expression of Il10 and proinflammatory cytokines, including Ifng in Th1 cells. We show that the transcription factors Blimp-1 and c-Maf each have unique and common effects on cytokine gene regulation and not only co-operate to induce Il10 gene expression in IL-12 plus IL-27 differentiated Th1 cells, but additionally directly negatively regulate key proinflammatory cytokines including Ifng, thus providing mechanisms for reinforcement of regulated Th1 cell responses.

2023-08-24 | GSE197782 | GEO

IL-27 driven transcriptional network identifies regulators of IL-10 expression across T helper cell subsets [IL10+ vs IL10-T helper cell RNA-seq]

Project description:IL-27 is an immunoregulatory cytokine that suppresses inflammation through multiple mechanisms including induction of IL-10, but the transcriptional network mediating its diverse functions remains unclear. Combining temporal RNA profiling with computational algorithms, we predict 79 transcription factors induced by IL-27 in T cells. We validate 11 known and discover 5 positive (Cebpb, Fosl2, Tbx21, Hlx, Atf3) and 2 negative (Irf9, Irf8) Il10 regulators, generating an experimentally refined regulatory network for Il10. We report two central regulators Prdm1 and Maf that cooperatively drive the expression of signature genes induced by IL-27 in Type 1 regulatory T cells, mediate IL-10 expression in all T helper cells, and determine the regulatory phenotype of colonic Foxp3+regulatory T cells. Prdm1/Maf double-knockout mice develop spontaneous colitis, phenocopying the ll10 deficient mice. Our work provides insights for IL-27 driven transcriptional networks and identifies two shared Il10 regulators that orchestrate immunoregulatory programs across T helper cell subsets.

2020-12-21 | GSE158703 | GEO

IL-27 driven transcriptional network identifies regulators of IL-10 expression across T helper cell subsets[Prdm1/Maf KO Tr1 ATAC-seq]

2020-12-21 | GSE158701 | GEO

IL-27 driven transcriptional network identifies regulators of IL-10 expression across T helper cell subsets[Tr1 differentiation with IL-27 microarray]

2020-12-21 | GSE159207 | GEO

IL-27 driven transcriptional network identifies regulators of IL-10 expression across T helper cell subsets[Prdm1/Maf KO colonic CD4 T cells scRNA-seq]

2020-12-21 | GSE158967 | GEO

IL-27 driven transcriptional network identifies regulators of IL-10 expression across T helper cell subsets[Tr1 deficient in TFs RNA-seq]

2020-12-21 | GSE158750 | GEO

IL-27 produced during acute malaria infection regulates Plasmodium-specific memory CD4+ T cells

Project description:Malaria infection elicits both protective and pathogenic immune responses, and IL-27 is a critical cytokine that regulate effector responses during infection. Here, we identified a critical window of CD4+ T cell responses that is targeted by IL-27. Neutralization of IL-27 during acute infection with Plasmodium chabaudi expanded specific CD4+ T cells, which were maintained at high levels thereafter. In the chronic phase, Plasmodium-specific CD4+ T cells in IL-27-neutralized mice consisted mainly of CD127+KLRG1- and CD127-KLRG1+ subpopulations that displayed distinct cytokine production, proliferative capacity and are maintained in a manner independent of active infection. Single cell RNA-seq analysis revealed that these CD4+ T cell subsets formed independent clusters that express unique Th1-type genes. These IL-27-neutralized mice exhibited enhanced cellular and humoral immune responses and protection. These findings demonstrate that IL-27, which is produced during the acute phase of malaria infection, inhibits the development of unique Th1 memory precursor CD4+ T cells, suggesting potential implications for the development of vaccines and other strategic interventions.

2023-10-19 | GSE225556 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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