Similar Datasets
Project description:Metabolic programs of immune cells are closely linked to their effector functions , where physiological molecules provide environmental cues and guidance. Exactly how it happens is still being unraveled. Insulin maintains normal blood glucose levels and glucose is themain source of energy and a precursor for many biomolecules in T cells, whereas γ-aminobutyric acid (GABA), best known as a neurotransmitter, is increasingly recognized as a regulatory molecule in the immune system. Here, we demonstrate that GABA-mediated reduction of metabolic activity and release of inflammatory molecules, including IFNγ and IL-10, was abolished in human CD4+ T cells, when the glucose concentration was elevated above normal levels. In a glucose concentration-dependent manner, insulin enhanced the GABAA receptors activated currents and GABA-dependent Ca2+ influx. GABA decreased, whereas insulin maintained glycolysis but in a SGLT (Na + -glucose transporter)-dependent manner, revealing expression of SGLTs in activated CD4+ T cells. The SGLTs antagonist phlorizin, alone or together with GABA, restored the inhibition of IFNγ and IL-10 release in presence of high glucose. This study exposes concerted effects of GABA, glucose and insulin on CD4+ T cells metabolic activity and release of inflammatory molecules, and identifies a role for SGLTs in CD4+ T cells function.
2024-08-10 | PXD041654 | Pride
Project description:GABA, glucose and insulin orchestrate CD4+ T cells effector functions
| PRJNA957262 | ENA
Project description:The mechanism of CD4(+) T cell depletion during chronic human immunodeficiency virus type 1 (HIV-1) infection remains unknown. Many studies suggest a significant role for chronic CD4(+) T cell activation. We assumed that the pathogenic process of excessive CD4(+) T cell activation would be reflected in the transcriptional profiles of activated CD4(+) T cells. Here we demonstrate that the transcriptional programs of in vivo activated CD4(+) T cells from untreated HIV(+) individuals are clearly different from those activated CD4(+) T cells from HIV(-) individuals. We observed a dramatic up-regulation of cell cycle-associated and interferon-stimulated transcripts in activated CD4(+) T cells of untreated HIV(+) individuals. Furthermore, we find an enrichment of proliferative and Type I interferon-responsive transcription factor binding sites in the promoters of genes that are differentially expressed in activated CD4(+) T cells of untreated HIV(+) individuals compared to HIV(-) individuals. We confirm these findings by examination of in vivo activated CD4(+) T cells. Taken together, these results suggest that activated CD4(+) T cells from untreated HIV(+) individuals are in a hyper-proliferative state that is modulated by Type I interferons. From these results, we propose a new model for CD4(+) T cell depletion during chronic HIV-1 infection. Keywords: disease state analysis
2008-02-19 | GSE9927 | GEO
Project description:The mechanism of CD4(+) T cell depletion during chronic human immunodeficiency virus type 1 (HIV-1) infection remains unknown. Many studies suggest a significant role for chronic CD4(+) T cell activation. We assumed that the pathogenic process of excessive CD4(+) T cell activation would be reflected in the transcriptional profiles of activated CD4(+) T cells. Here we demonstrate that the transcriptional programs of in vivo activated CD4(+) T cells from untreated HIV(+) individuals are clearly different from those activated CD4(+) T cells from HIV(-) individuals. We observed a dramatic up-regulation of cell cycle-associated and interferon-stimulated transcripts in activated CD4(+) T cells of untreated HIV(+) individuals. Furthermore, we find an enrichment of proliferative and Type I interferon-responsive transcription factor binding sites in the promoters of genes that are differentially expressed in activated CD4(+) T cells of untreated HIV(+) individuals compared to HIV(-) individuals. We confirm these findings by examination of in vivo activated CD4(+) T cells. Taken together, these results suggest that activated CD4(+) T cells from untreated HIV(+) individuals are in a hyper-proliferative state that is modulated by Type I interferons. From these results, we propose a new model for CD4(+) T cell depletion during chronic HIV-1 infection. Experiment Overall Design: This experiment compares the expression of CD4+ T-cells obtained from 11 HIV+ individuals with that from comparable 9 HIV- control individuals. Each individual's cells were analyzed on separate single-color chips, and the average values of both biological replicate groups were analyzed for statistical significance. Experiment Overall Design: The biological significance of up- and down-regulated probesets/genes was analyzed using the Gene Ontology annotation dataset.
2008-04-07 | E-GEOD-9927 | biostudies-arrayexpress
Project description:MRL/Faslpr mice is a lupus prone strain that exhibits lupus disease features at 12-16 weeks of age, including high-titer circulating anti-DNA antibodies, splenomegaly, lymphadnopathy, skin lesions, and IgG deposits in the kidney. At 16-24 weeks of age, CD4+ B220- CD44+ T cells were sorted into three populations based on the expression of two cell surface molecules, CD62L and PSGL1. CD62Lhi PSGL1hi, CD62Llo PSGL1hi, and CD62Llo PSGL1lo CD4+ T cells were isolated directly ex vivo. There was no treatment given to the animals. Naive (CD62Lhi CD44lo) CD4+ B220- T cells were isolated from young 6-8 week old female mice for comparison. We used a microarray to identify unique features of the CD62Llo PSGL1lo population in comparison to naïve CD4+ T cells and other activated CD4+ T cells. Cells were isolated from the spleens of aged (16-24 weeks) female MRL/Faslpr mice directy ex vivo, and immediatley sorted into 3 populations; CD62Lhi PSGL1hi, CD62Llo PSGL1hi, and CD62Llo PSGL1lo. All 3 populations of cells were previously gated on TCRb+, CD4+, B220-, CD44+. Naive CD4 T cells were isolated directly ex vivo from the spleens of young (6-8 weeks) female MRL/Faslpr mice, and immediately sorted by gating on TCRb+, CD4+, B220-, CD62Lhi, CD44lo. Three indepedent sorts were performed. RNA was isolated using Qiagen's RNAeasy kit and total RNA was submitted to the W.M. Keck Foundation Biotechnology Resource Laboratory at Yale for amplification and hybridization to Affymetrix Mouse Genome 430 2.0 GeneChips.
2010-03-18 | E-GEOD-20735 | biostudies-arrayexpress
Project description:Infection with cytomegalovirus is characterised by very strong and sustained T cell responses in peripheral blood. These expansions increase even further with age and research suggests CMV-specific T cells may contribute towards development of accelerated immune senescence and vascular disease in elderly people. In this study we compared the transcriptional profile of CD4+ T cells specific for two CMV-derived epitopes to that of CD4+CCR7-CD45RA- (effector memory) T cells of CMV-seronegative individuals. The aim was to get a better understanding of the nature of these virus-specific T cells and how they may contribute to immunopathology.
2016-08-07 | E-MTAB-4510 | biostudies-arrayexpress
Project description:RNA expression in CD4 positive naïve and dendritic cell-activated T cells
2020-11-24 | GSE120277 | GEO
Project description:Variation in individuals' adaptive immune response is believed to influence susceptibility to complex diseases in humans. The genetic basis of such variation is poorly understood. We measured gene expression from resting and activated CD4+ T cells derived from the peripheral blood of healthy individuals. We activated the primary T cells with anti-CD3/CD28 beads alone or with IFNb or Th17 polarizing cytokines.
2014-08-28 | GSE60234 | GEO
Project description:CD4+ T cells specific for commensal bacterial antigens are expanded in inflammatory bowel disease (IBD) patients compared to healthy individuals. How and where commensal-specific CD4+ T cells get activated is yet to be fully understood. We used TCR-transgenic CD4+ T cells specific to a commensal bacterial antigen (CBir1 T cells) and the dextran sulfate sodium (DSS) model of IBD to characterize how and where the activation of commensal-specific CD4+ T cells occurs. We found that CBir1 T cells proliferate following intestinal damage and cognate antigen presentation is mediated by CD11c+ cells in the colon-draining mesenteric lymph nodes (cMLNs). Using assay for transposase-accessible chromatin sequencing (ATAC-seq) and flow cytometry, we showed that activated CBir1 T cells preferentially acquire an effector rather than regulatory phenotype, which is plastic over time.
2023-11-15 | GSE247375 | GEO
Project description:MRL/Faslpr mice is a lupus prone strain that exhibits lupus disease features at 12-16 weeks of age, including high-titer circulating anti-DNA antibodies, splenomegaly, lymphadnopathy, skin lesions, and IgG deposits in the kidney. At 16-24 weeks of age, CD4+ B220- CD44+ T cells were sorted into three populations based on the expression of two cell surface molecules, CD62L and PSGL1. CD62Lhi PSGL1hi, CD62Llo PSGL1hi, and CD62Llo PSGL1lo CD4+ T cells were isolated directly ex vivo. There was no treatment given to the animals. Naive (CD62Lhi CD44lo) CD4+ B220- T cells were isolated from young 6-8 week old female mice for comparison. We used a microarray to identify unique features of the CD62Llo PSGL1lo population in comparison to naïve CD4+ T cells and other activated CD4+ T cells.
2010-03-18 | GSE20735 | GEO