Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA213981 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:A transgenic mouse was generated using a CD2-driven transgene containing the cDNA of Ppp2ca to achieve over-expression of PP2Ac in T cells. Naïve CD4 T cells were isolated and lysed at times 0, 6, and 24 hours after stimulation with anti-CD3 and anti-CD28
2013-08-02 | GSE49466 | GEO
Project description:A transgenic mouse was generated using a CD2-driven transgene containing the cDNA of Ppp2ca to achieve over-expression of PP2Ac in T cells. Naïve CD4 T cells were isolated and lysed at times 0, 6, and 24 hours after stimulation with anti-CD3 and anti-CD28 Naïve CD4 T cells from wild type mice were compared with naïve CD4 T cells from PP2Ac transgenic mice
2013-08-02 | E-GEOD-49466 | biostudies-arrayexpress
Project description:Cold-inducible RNA-binding protein (CIRP) is a ubiquitous intracellular RNA chaperon, which serves as a damage-associated molecular pattern (DAMP) when released outside the cells upon stimulation by inflammation and infection. It has been shown that CIRP promotes splenic CD4+ and CD8+ T-cell activation in vivo and predisposes CD4+ T cells to a Th1 hyperinflammatory response profile in vitro. However, the effect and underlying mechanisms of CIRP on Th17/Treg differentiation is still unclear. This study reveals the transcriptomic changes of mouse Naïve CD4+ T cells induced by Recombinant Mouse CIRP (rmCIRP) in vitro.
2023-06-30 | GSE234044 | GEO
Project description:Protein phosphatase 2A (PP2A) is one of the most common serine/threonine phosphatases in mammalian cells and primarily functions to regulate cell signaling, glycolipid metabolism, and apoptosis. Its PP2A catalytic subunit (PP2Ac) plays an important role in its function. Nonetheless, at present, there are only a few reports on the regulatory role of PP2Ac in pancreatic β-cells under lipotoxicity. Mouse pancreatic insulinoma (MIN6) cells were transfected by lentiviruses to generate PP2Ac knockdown cells and incubated with palmitate (PA) to establish the lipotoxicity model. Serine/Threonine Phosphatase Assay System kit, Cell Counting Kit-8 (CCK-8), flow cytometry, enzyme-linked immunosorbent assay (ELISA), Western Blotting (WB) and other techniques were used to measure PP2A activity, cell viability, apoptosis, oxidative stress, and insulin secretion. An animal model of lipotoxicity with knockdown of PP2Ac was established by a high-fat diet (HFD) after using adeno-associated viruses (AAV) to interfere with PP2Ac expression in mouse pancreatic tissues. Serine/Threonine Phosphatase Assay System kit, ELISA, pancreatic tissue immunofluorescence and other techniques were used to measure PP2A activity in pancreatic tissue, serum insulin level and the proliferation of mouse pancreatic β-cells. We found that PP2Ac knockdown inhibited lipotoxicity-induced PP2A hyperactivation, increased the resistance of pancreatic β-cells to lipotoxicity, decreased PA-induced apoptosis in MIN6 cells, protected the function of both the endoplasmic reticulum (ER) and mitochondria, and improved insulin secretion. By mRNA sequencing and Western blotting analysis, we hypothesized that the protective effects of PP2Ac knockdown in MIN6 cells may be mediated by the MAPK pathway. Moreover, the results obtained from animal experiments suggest that the specific knockdown of pancreatic PP2Ac could effectively attenuate HFD-induced insulin resistance and reduce the compensatory proliferation of pancreatic β-cells in mice. The present study revealed the effects and mechanisms of interfering with PP2Ac gene expression on pancreatic β-cells in vivo and in vitro, which might provide insights for the treatment of type 2 diabetes in the clinic.
2023-09-13 | GSE242538 | GEO
Project description:Cell intrinsic changes in transcription of naïve CD4 T cells upon S1pr1 deletion
| PRJNA381079 | ENA
Project description:Ascertain the effects of disease-causing gene mutations on the differentiation status of human naïve CD4+ T cells in the setting of primary immunodeficiencies. Thus, do CD4+ T cells isolated according to a naïve surface phenotype (ie CD4+CD45RA+CCR7+) from healthy donors exhibit a similar gene expression profile as phenotpyically-matched cells isolated from individuals with defined primary immunodeficiencies caused by specific monogenic mutations.
2016-06-29 | GSE81408 | GEO
Project description:The epigenetic determinants driving the rapid responses of memory CD4 T cells to antigen are currently an area of active research. While much has been done to characterize various Th subsets and their associated genome-wide epigenetic patterns, the dynamics of histone modifications during CD4 T cell activation and the differential kinetics of these epigenetic marks between naïve and memory T cells have not been evaluated. In this study we have detailed the dynamics of genome-wide promoter H3K4me2 and H3K4me3 over a time course during activation of human naïve and memory CD4 T cells. Our results demonstrate that changes to H3K4 methylation predominantly occur relatively late after activation (120 hours) and reinforce activation-induced upregulation of gene expression affecting multiple pathways important to T cell activation, differentiation, and function. The dynamics and mapped pathways of H3K4 methylation are distinctly different in memory cells. Memory CD4 have substantially more promoters marked by H3K4me3 alone, and that is influenced by promoter CpG content, reinforcing their more differentiated state. Our study provides the first data examining genome-wide histone modification dynamics during T cell activation, providing insight into the cross-talk between H3K4 methylation and gene expression, and underscoring the impact of these marks upon key pathways integral to CD4 T cell activation and function.
2016-06-01 | GSE73213 | GEO
Project description:The epigenetic determinants driving the rapid responses of memory CD4 T cells to antigen are currently an area of active research. While much has been done to characterize various Th subsets and their associated genome-wide epigenetic patterns, the dynamics of histone modifications during CD4 T cell activation and the differential kinetics of these epigenetic marks between naïve and memory T cells have not been evaluated. In this study we have detailed the dynamics of genome-wide promoter H3K4me2 and H3K4me3 over a time course during activation of human naïve and memory CD4 T cells. Our results demonstrate that changes to H3K4 methylation predominantly occur relatively late after activation (120 hours) and reinforce activation-induced upregulation of gene expression affecting multiple pathways important to T cell activation, differentiation, and function. The dynamics and mapped pathways of H3K4 methylation are distinctly different in memory cells. Memory CD4 have substantially more promoters marked by H3K4me3 alone, and that is influenced by promoter CpG content, reinforcing their more differentiated state. Our study provides the first data examining genome-wide histone modification dynamics during T cell activation, providing insight into the cross-talk between H3K4 methylation and gene expression, and underscoring the impact of these marks upon key pathways integral to CD4 T cell activation and function.
2016-06-01 | GSE73212 | GEO
Project description:Objective. TNF? is a potent pro-inflammatory cytokine playing a pivotal role in several autoimmune diseases. Neutralizing TNF? inhibits T cell proliferation and IFN? production, and enhances suppressive capacity of regulatory T cells (Treg). Little is known about the mechanism of TNF? blocking agents on naïve T cell differentiation. Methods. Naïve CD4+ T cells were activated by dendritic cells (DC) in presence or absence of anti-TNF? agents. T cell polarization and activation was assessed during T cell differentiation. In addition, whole genome gene expression analysis was performed on anti-TNF?-treated T cells. Results. Neutralizing TNF? during priming of naïve CD4+ T cells by DC favors development of IL-10+ T helper (Th) cells at the expense of IFN? induction. TNF? inhibits IL-10 via TNFRII, which becomes expressed after naïve T cell activation. While initial CD4+ T cell activation was not affected, neutralization of TNF? negatively affected later stages of T cell priming by counteracting full T cell activation and survival. Whole genome gene expression analysis revealed a regulatory gene profile of anti-TNF?-treated T cells. Indeed, neutralizing TNF? during naïve T cell priming enhanced the suppressive function of anti-TNF?-treated T cells. Conclusion. Inhibition of TNF?–TNFRII interaction affects late stage effector T cell development and shifts the balance of Th cell differentiation towards IL-10 expressing regulatory T cells, which may be one of the beneficial mechanisms in TNF? blocking therapies. Naïve CD4+ T cells were CFSE labeled and co-cultured for 13 days with allogeneic dendritic cells in the presence or absence of anti-TNF? agents. After 13 days, the CFSElow T cells were FACS sorted. Samples were generated from three independent donors.
2014-06-25 | E-GEOD-42812 | biostudies-arrayexpress
Project description:Memory T cells are primed for rapid responses to antigen; however, the molecular mechanisms responsible for priming remain incompletely defined. CpG methylation in promoters is an epigenetic modification, which regulates gene transcription. Using targeted bisulfite sequencing, we examined methylation of 2100 genes (56,000 CpG) mapped by deep sequencing to T cell activation in human naïve and memory CD4 T cells. 466 CpGs (132 genes) displayed differential methylation between naïve and memory cells. 21 genes exhibited both differential methylation and gene expression before activation, linking promoter DNA methylation states to gene regulation; 6 genes encode proteins closely studied in T cells while 15 genes represent novel targets for further study. 39 genes exhibited reduced methylation in memory cells coupled with increased gene expression with activation compared to naïve cells, revealing specific genes more rapidly expressed in memory compared to naïve cells and potentially regulated by DNA methylation. These findings define a DNA methylation signature unique to memory CD4 T cells and correlated with activation-induced gene expression. transcriptome of primary human naïve and memory CD4 T cells at rest and 48 hours post-activation.
2015-01-20 | E-GEOD-58684 | biostudies-arrayexpress