Differential transcriptome analysis of naïve T cell activtion, TH1 cell differentiation and TH1 cell reactivation
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE222902 | GEO | 2024/04/30
REPOSITORIES: GEO
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Project description:Differential transcriptome analysis of naïve T cell activtion, TH1 cell differentiation and TH1 cell reactivation
| PRJNA923806 | ENA
Project description:The differentiation of human CD4+ T cells into different subtypes of T helper cells and regulatory T cells is crucial for an appropriate immunological response. Among all subtypes Th1 cells are the most prominent specific cell type, representing about 50% of all lymphocytes. So far most global proteomic studies have used either only partially purified T helper cell subpopulations and/or have employed artificial protocols for inducing specific T helper cell subtypes and/or applied gel based approaches. These studies have shed light on molecular details of certain aspects of the proteome. Nevertheless a more global analysis of highly pure primary naïve and Th1 cells by LC-MS/MS is needed in order to contribute to the proteome based T cell subtype characterization. We were able to identify 1757 proteins in total, out of which 49 were significantly regulated. The utilization of highly purified Th1 cells for a global proteome assessment and the bioinformatical comparison to naïve cells reveals the relevance of changes in the metabolism and the ubiquitination pathways upon T cell differentiation.
2015-10-13 | PXD001066 | Pride
Project description:ATAC-Seq experiments were performed to elucidate the chromatin state changes among naïve CD4+ T cells, WT follicular helper T (TFH) cells and WT type 1 helper T (TH1) cells Day2 (D2), Day5 (D5), Day8 (D8) post-LCMV-Armstrong infection, as well as EZH2-null (KO) TFH and TH1 at Day8 post-LCMV-infection. The analysis suggested stringent lineage-specific mode of chromatin accessibility in each group, indicating chromatin remodeling is tightly associated with TFH versus TH1 lineage differentiation in response to acute viral infection. Furthermore, the comparison between wild-type and EZH2-null TFH cells showed that less-opening state of certain chromatin accessible region in TFH-differentiation associated genes in the formers, suggesting EZH2 led to permissive chromatin accessibility primarily at specific regions of TFH-associated genes. H3K27me3-ChIP-seq was performed in WT TFH and TH1 cells to confirm the deposition of the histone marks at those loci.
2018-12-31 | GSE120532 | GEO
Project description:Gene expression profiling of repeatedly activated compared to recently activated Th1 cells to identify genes that play a role in chronic inflammatory disorders and may qualify as diagnostic or therapeutic targets; ; Upon activation under appropriate costimulatory conditions, naive T helper (Th) cells differentiate into Th2 or Th17 cells, each characterized by the expression of specific effector cytokines. In response to a repeated stimulation with antigen, Th cells develop a stable memory for the expression of those cytokines as well as for other secreted or membrane-associated factors. The stable memory for the expression of proinflammatory effector functions may explain the resistance of Th effector cells to conventional immunosuppressive therapy, and the inability of immunosuppression to cure chronic inflammation. The imprinting of the functional memory is based on epigenetic modifications and expression of distinct transcription factors. In this project, we compare the transcriptomes of once and repeatedly activated murine Th1 cells, to identify genes that induce and maintain the functional memory and control the persistence of pathogenic memory Th1 cells. This in turn might help to discriminate pathogenic versus protective cells in immunopathology and present novel targets for the diagnosis and therapy of chronic inflammatory disease. Experiment Overall Design: Genes differentially expressed in once versus four times stimulated Th1 cells. In vitro polarization of murine naïve DO11.10 T cells towards Th1 direction (5 ng/ml recombinant murine IL-12, 5 μg/ml anti-IL-4 antibody) with antigenic stimulation (ova323-339 and irradiated splenic APCs). The transcriptional profiles of resting one week old Th1 (Th1 1w) cells and resting 4 week old Th1 (Th1 4w) cells were compared using Affymetrix Murine Genome (MG) U74V2A GeneChip arrays. Experiment Overall Design: 10 µg of total RNA from each cell sample was reverse transcribed using T7-(d)T24 primer and SuperScript II reverse transcriptase Experiment Overall Design: cDNA extraction with a PhaseLock gel (Eppendorf), and precipitation with ethanol and ammonium acetate Experiment Overall Design: Biotinylated cRNA was transcribed with the MEGAscript high yield transcription kit (Ambion), fragmented, and the hybridization cocktail was prepared (15 µg fragmented biotin-labeled cRNA spiked with Eukaryotic Hybridization control) Experiment Overall Design: probes were subsequently hybridised with the GeneChip U74Av2 for 16 hrs at 45 oC Experiment Overall Design: after washing the hybridisation signals were visualised by staining with streptavidin-phycoerythrin and amplification with an anti-streptavidin antibody Experiment Overall Design: TH1_1w_C1; TH1_1w_C2; TH1_1w_C3TH1_4w_C1; TH1_4w_C2; TH1_4w_C3 Experiment Overall Design: 1w: 1 week in culture; 4w: 4 weeks in culture; C1-3: Culture or Experiment No.
2008-06-18 | E-GEOD-11534 | biostudies-arrayexpress
Project description:Microarray experiments were performed to demonstrate the transcriptome changes due to Rictor deficiency in memory follicular T helper (Tfh) and Type 1 T helper (Th1) cells. These data revealed that the immunological memory formation and persistance associated genes are changed in Rictor-null memory Tfh and Th1 cells, indicating that Rictor is essential for memory CD4 T cell pool.
2021-06-06 | GSE151800 | GEO
Project description:T helper cell subsets have unique calcium (Ca2+) signals when activated with identical stimuli. The regulation of these Ca2+ signals and their correlation to the biological function of each T cell subset remains unclear. Trpm4 is a Ca2+-activated cation channel that we found is expressed at higher levels in Th2 cells compared to Th1 cells. Inhibition of Trpm4 expression increased Ca2+ influx and oscillatory levels in Th2 cells and decreased influx and oscillations in Th1 cells. This inhibition of Trpm4 expression also significantly altered T cell cytokine production and motility. Our experiments revealed that decreasing Trpm4 levels divergently regulates nuclear localization of NFAT. Consistent with this, gene profiling did not show Trpm4 dependent transcriptional regulation and T-bet and GATA-3 levels remain identical. Thus, Trpm4 is expressed at different levels on T helper cells and plays a distinctive role in T cell function by differentially regulating Ca2+ signaling and NFAT localization. T helper cell gene expression levels when Trpm4 is inhibited by siRNA or dominant negative Trpm4 construct. The ion channel Trpm4 was inhibited in Th1 or Th2 cells using either siRNA or a dominant negative Trpm4 retrovirus and changes in gene profiles were analyzed.
2013-01-23 | E-GEOD-21996 | biostudies-arrayexpress
Project description:Respiratory Syncytial Virus (RSV) is a leading cause of morbidity and mortality in children, due in part to their distinct immune system, characterized by impaired induction of T-helper 1 (Th1)‐immunity. Here we describe cationic adjuvant formulation (CAF)-08, a liposomal vaccine formulation tailored to induce Th1 immunity in early life via synergistic engagement of Toll-like Receptor 7/8 and the C-type lectin receptor Mincle. Quantitative phosphoproteomics applied to human dendritic cells revealed a key role for Protein Kinase C- for enhanced Th1 cytokine production in neonatal dendritic cells and identified signaling events resulting in antigen cross-presentation. In vivo, a single immunization at birth with CAF08-adjuvanted RSV pre-fusion antigen protected newborn mice from RSV infection through induction of antigen-specific CD8+ and Th1 cells. Overall, we describe a novel pediatric adjuvant formulation and characterize its mechanism of action providing a promising avenue for development of early life vaccines against RSV and other intracellular pathogens.
2022-06-14 | PXD025568 | Pride
Project description:Differentiation of naive CD4+ T cells into T-helper (Th) effector subsets is critical for protection against pathogens. Together, E-protein transcription factors and the inhibitor-of-DNA binding (Id) proteins are important arbiters of T cell development, but their role in the differentiation of Th1 and Tfh cells is not well understood. Th1 cells show robust Id2 expression compared to Tfh cells, and RNAi depletion of Id2 increased Tfh cell frequencies and germinal center responses, while impairing Th1 cell accumulation during viral infection. Further, Th1 cell differentiation was blocked by genetic ablation of Id2, leading to E-protein dependent accumulation of effector cells with 78% of Th1-associated genes showing diminished expression and a concurrent enrichment of the Tfh gene-expression program. The Tfh-defining transcriptional repressor Bcl6 bound to the Id2 locus inhibiting expression, providing a mechanism by which bimodal expression of Id2 in Tfh and Th1 cells can be established. Thus, Id2 is critical in enforcing the reciprocal development of Th1 and Tfh cell fates. We used microarray to assess the changes in gene expression between Id2-sufficient and -deficient Th1 and Tfh cells.
2016-05-23 | GSE74854 | GEO
Project description:Naïve CD4 T cells are traditionally viewed as a quiescent, homogeneous, resting population, but merging evidence reveals their heterogeneity, which can be crucial for understanding disease contexts and therapeutic outcomes. In this study, we identify distinct subpopulations within both murine and human naïve CD4 T cells by single cell-RNA-sequencing (scRNA-seq), particularly focusing on a subpopulation that expresses super-high levels of interleukin-7 receptor (IL-7Rsup-hi), along with CD97, IL-18R, and Ly6C. This subpopulation, absent in the thymus and peripherally induced, exhibits type 1 helper T cell (Th1)-poised characteristics and plays a role in inhibiting cancer progression in mouse B16F10 tumor model. In humans, this IL-7Rsup-hi subpopulation expressing CD97 correlates with responsiveness to anti-PD-1 therapy in cancer patients and disease state of multiple sclerosis. By elucidating the heterogeneity of naive CD4 T cells, including a Th1-poised subpopulation capable of robust type 1 responses, we highlight the importance of this heterogeneity in inflammatory conditions for defining the disease states and predicting drug responsiveness.
2025-02-10 | GSE285018 | GEO
Project description:T-helper cells differentiate from naïve precursors into multiple lineages, including Th1, Th2, Th17 and inducible Treg, in humans and mice. The identification of each lineage is currently determined by examination of a small number of genes encoding hallmark cytokines and/or transcription factors in both species To gain a better understanding of human T-helper cell function we have performed detailed transcriptional profiling of highly polarized Th1 and Th2 cells in both resting and activated states examining gene and miRNA expression Naïve CD4 positive T-cells were isolated from peripheral blood of three different human donors. Cells were differenitated into Th1 and Th2 cells in vitro for 28 days to achieve homogeneous cell lineages. Samples were taken at resting state or activated for 4 hours with PMA/Ionomycin.
2016-08-01 | E-GEOD-43769 | biostudies-arrayexpress