Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

ZEB2 orchestrates a transcriptional program to safeguard the integrity of human CD4+ Th1 EM cells

ABSTRACT: CD4+ Th1 cells migrate to sites of inflammation, where they are indispensable for eliminating intracellular pathogens. The lineage defining transcription factor T-bet establishes the Th1 transcriptional programme, directing IFNG to drive effector responses and inducing subordinate transcription factors to shape their phenotype. Aberrant Th1 cell activity drives the pathogenesis of multiple autoimmune diseases, but the detailed mechanisms by which Th1 cells maintain or lose their integrity remain largely uncharacterised. Using immunogenomics and high resolution immune phenotyping in human CD4+ cells, we discovered that the transcription factor ZEB2 is lineage restricted to Th1EM cells. Detailed molecular validation using CRISPR/Cas9 deletion of ZEB2, whole genome transcriptomics and pathway mapping has revealed that ZEB2 is a signalling hub for multiple pathways, stabilising the integrity and function of human CD4+ Th1EM cells. Furthermore, our disease linked pathway mapping suggests that ZEB2 is implicated in the control of Th1-mediated autoimmune disease.

ORGANISM(S): Homo sapiens

PROVIDER: GSE254977 | GEO | 2024/08/31

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Retinoic acid signaling constrains the plasticity of Th1 cells and prevents development of pathogenic Th17 cells [ChIP-Seq experiments]

Project description:CD4+ T cells differentiate into phenotypically distinct T-helper cells upon antigenic stimulation. Regulation of plasticity between these CD4+ T-cell lineages is critical for immune homeostasis and prevention of autoimmune diseases. However, the factors that regulate lineage stability are largely unknown. Here we investigate a role for retinoic acid (RA) in the regulation of lineage stability using T helper 1 (Th1) cells, traditionally considered the most phenotypically stable Th subset. We found that RA, through its receptor RARa, sustains stable expression of Th1 lineage specifying genes as well as repressing genes that instruct Th17 cell fate. RA signaling is essential for limiting Th1 cell conversion into Th17 effectors and for preventing pathogenic Th17 responses in vivo. Our studies identify RA-RARa as a key component of the regulatory network governing Th1 cell fate and define a new paradigm for the development of pathogenic Th17 cells. These findings have important implications for autoimmune diseases in which dysregulated Th1-Th17 responses are observed. Identification of RARa binding in wild-type Th1 cells and mapping of enhancers using chromatin IP against p300, H3k4me1, H3k4me3, and H3k27ac in wild-type and dnRara Th1 cells.

2015-03-10 | E-GEOD-60353 | biostudies-arrayexpress

ZEB2 orchestrates a transcriptional program to safeguard the integrity of human CD4+ Th1 EM cells

Project description:ZEB2 orchestrates a transcriptional program to safeguard the integrity of human CD4+ Th1 EM cells

| PRJNA1072732 | ENA

Puniya2021 - CD4+ Th1 cell metabolic model

Project description:CD4+ T cells are critical components in the human immune system. They produce cytokines to fight against pathogens and abnormal cells and stimulate other cells, such as B cells, macrophages, and neutrophils, to generate an immune response. T helper 1 (Th1) cells are subtypes of CD4+ T cells that differentiate from naive CD4+ T cells in a specific cytokine environment. The Th1 cell model consists of 3956 reactions, 2517 metabolites, and 1133 genes. CD4+ T cell models helped identify drug targets and repurposable drugs against autoimmune diseases.

2022-06-14 | MODEL1909260004 | BioModels

Puniya2021 - Naive CD4+ T cell metabolic model

Project description:CD4+ T cells are critical components in the human immune system. They produce cytokines to fight against pathogens and abnormal cells and stimulate other cells, such as B cells, macrophages, and neutrophils, to generate an immune response. Naive CD4+ T cells are precursor cells that can differentiate into T helper - 1, - 2, - 17 (Th1, Th2, Th17) and regulatory T cells (Tregs) subtypes based on the type of pathogens or disease. The naive CD4+ T cell model consists of 5179 reactions, 3153 metabolites, and 1055 genes. Together with Th1, Th2, and Th17 models, the naive CD4+ T cell model helped identify drug targets and repurposable drugs against autoimmune diseases.

2023-11-27 | MODEL1909260003 | BioModels

Transcriptional profiling of CD4+ T cells with high, intermediate and low PD-1 and ICOS co-expression from HCV infected chimpanzees

Project description:A sustained CD4+ T cell response is required for resolution of acute HCV infection but remains poorly characterized. Here, CD4+ T cells with high PD-1 and ICOS co-expression expanded in the blood of chimpanzees during acute HCV infection. The peak response was comprised primarily of HCV-specific populations and temporally associated with acute hepatitis, seroconversion, and initial control of HCV replication. Circulating PD-1hiICOShi CD4+ T cells differentially expressed genes associated with Tfh, Th1, and cytotoxic signatures. Co-production of Tfh (CXCL13, IL-21) and Th1 (IFN-) effector molecules was observed after HCV antigen stimulation. HCV-specific Tfh1 CD4+ T cells infiltrated liver, consistent with expression of chemokine receptors that mediate homing to inflamed tissues. Most were CXCR5-negative and therefore resembled Tph/Tfhx13 CD4+ T cells recently described in cancer and autoimmune conditions. Detailed transcriptional, phenotypic, and functional analysis of the protective CD4+ T cell response presented here is expected to aid HCV vaccine development.

2024-11-14 | GSE247812 | GEO

Retinoic acid signaling constrains the plasticity of Th1 cells and prevents development of pathogenic Th17 cells [Affymetrix experiments]

Project description:CD4+ T cells differentiate into phenotypically distinct T-helper cells upon antigenic stimulation. Regulation of plasticity between these CD4+ T-cell lineages is critical for immune homeostasis and prevention of autoimmune diseases. However, the factors that regulate lineage stability are largely unknown. Here we investigate a role for retinoic acid (RA) in the regulation of lineage stability using T helper 1 (Th1) cells, traditionally considered the most phenotypically stable Th subset. We found that RA, through its receptor RARa, sustains stable expression of Th1 lineage specifying genes as well as repressing genes that instruct Th17 cell fate. RA signaling is essential for limiting Th1 cell conversion into Th17 effectors and for preventing pathogenic Th17 responses in vivo. Our studies identify RA-RARa as a key component of the regulatory network governing Th1 cell fate and define a new paradigm for the development of pathogenic Th17 cells. These findings have important implications for autoimmune diseases in which dysregulated Th1-Th17 responses are observed. IFN-gamma+ Th1 cells from IFNgeYFP reporter mouse; comparing dnRARa to WT

2015-03-10 | E-GEOD-60354 | biostudies-arrayexpress

P2X7 signaling drives Th1 cell differentiation through metabolic reprogramming for aerobic glycolysis

Project description:This study provides evidence on the molecular mechanisms by which P2RX7 signaling promotes Th1 cell differentiation. P2RX7 induces T-bet expression and aerobic glycolysis in splenic CD4+ T cells that respond to malaria, at a time prior to Th1/Tfh polarization. Cell-intrinsic P2RX7 signaling sustains the glycolytic pathway and causes bioenergetic mitochondrial stress in activated CD4+ T cells. We also show in vitro the phenotypic similarities of Th1-polarized CD4+ T cells that do not express P2RX7 and those in which the glycolytic pathway is pharmacologically inhibited. In addition, ATP synthase blockade in vitro and the consequent inhibition of oxidative phosphorylation, which forces cells to use aerobic glycolysis, is sufficient to promote rapid CD4+ T cell proliferation and polarization to the Th1 profile in the absence of P2RX7. These data demonstrate that P2RX7-mediated metabolic reprograming for aerobic glycolysis is a key event for Th1 cell differentiation and suggest that ATP synthase inhibition is a fundamental mechanism by which P2X7 signaling induces the Th1 response.

2023-03-08 | PXD037754 | Pride

Impact of Acute methionine restriction on proteome of Th1 cells - Part 2

Project description:CD4 T cells were activated using CD3/CD28 antibodies in the presence of IL2 and IL12, to generate Th1 cells. Th1 cells were maintained and expanded in IL2 and IL12, on D5 Th1 cells were sorted for CD4+ expression and DAP1 exclusion. After flow sorting, live TH1 cells were resuspended (1e6 per ml) in methionine free RPMI, supplemented with 10% dialysed FBS, IL2 and IL12, and with L-methionine (100μM, or 1μM). Cells were cultured for 5 hrs before collection for proteomics processing.

2019-03-29 | PXD012053 | Pride

Retinoic acid signaling constrains the plasticity of Th1 cells and prevents development of pathogenic Th17 cells [Affymetrix experiments]

2015-03-10 | GSE60354 | GEO

Retinoic acid signaling constrains the plasticity of Th1 cells and prevents development of pathogenic Th17 cells [ChIP-Seq experiments]

2015-03-10 | GSE60353 | GEO