Browse
Submit Data
Databases
API
Help

Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Direct regulation of T cell exhaustion by NFAT [ChIP-Seq]

ABSTRACT: During persistent antigen stimulation, CD8+ cytolytic T cells (CTL) show a gradual decrease in effector function, or “exhaustion”, which impairs the immune response to tumors and infections. Here we show that NFAT, a transcription factor with an established role in T cell activation, in parallel controls a second transcriptional program conferring the characteristic features of CD8+ T cell exhaustion, including upregulation of genes encoding inhibitory cell surface receptors and diminished TCR signaling. Expression of an engineered NFAT1, which induces this negative regulatory program in the absence of the effector program, interferes with the ability of CD8+ T cells to protect against Listeria infection or attenuate tumor growth in vivo. NFAT elicits this second program of gene expression in large part by binding to a subset of the sites occupied by NFAT during a typical effector response, suggesting that a balance between the two pathways determines the outcome of TCR signaling. Determination of NFAT1 binding sites in CD8 T cells in vitro

ORGANISM(S): Mus musculus

SUBMITTER: Tarmo Äijö

PROVIDER: E-GEOD-64407 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

Direct regulation of T cell exhaustion by NFAT [RNA-Seq]

Project description:During persistent antigen stimulation, CD8+ cytolytic T cells (CTL) show a gradual decrease in effector function, or “exhaustion”, which impairs the immune response to tumors and infections. Here we show that NFAT, a transcription factor with an established role in T cell activation, in parallel controls a second transcriptional program conferring the characteristic features of CD8+ T cell exhaustion, including upregulation of genes encoding inhibitory cell surface receptors and diminished TCR signaling. Expression of an engineered NFAT1, which induces this negative regulatory program in the absence of the effector program, interferes with the ability of CD8+ T cells to protect against Listeria infection or attenuate tumor growth in vivo. NFAT elicits this second program of gene expression in large part by binding to a subset of the sites occupied by NFAT during a typical effector response, suggesting that a balance between the two pathways determines the outcome of TCR signaling. Understanding the role of CA-RIT-NFAT1 in T cells

2015-02-13 | E-GEOD-64408 | biostudies-arrayexpress

Direct regulation of T cell exhaustion by NFAT [RNA-Seq]

2015-02-13 | GSE64408 | GEO

Direct regulation of T cell exhaustion by NFAT [ChIP-Seq]

2015-02-13 | GSE64407 | GEO

Transcriptome differences in HCC infiltrated CD8+ T cells in effector and exhaustion state

Project description:CD8+ T cells isolated from HCC tissue were divided into three groups: PD1-TIM3- CD8+ TILs, exhibiting full effector function; PD1-intTIM3+ CD8+ TILs, exhibiting partial exhaustion; and PD1-hiTIM3+ CD8+ TILs, exhibiting severe exhaustion, as reflected by the differences in their ability to produce effector cytokines respectively. Transcriptome sequence analysis was performed to investigate the gene expression profile was performed.

2019-12-31 | E-MTAB-7278 | biostudies-arrayexpress

Genome wide mapping of NFAT1 binding sites in dendritic cells and of chromatin state in steady and dectin-1 activated dendritic cell line D1

Project description:We generated genome-wide chromatin-state maps of mouse dendritic cells in steady and dectin-1 activated with or without NFAT inhibitor FK506. We found the differential H3K4me3 signatures in these cells. This study provides the epigenetic signatures of steady, dectin-1activated with or without NFAT inhibition. We also generated stable dendritic cell line D1 expressing a V5 tagging NFAT1. This cell line was used to map the global binding sites of NFAT1 upon dectin-1 activation with 10ug/ml curdlan for 30 minutes. examine NFAT1-v5 genome wide binding sites and differential H3K4me3 epigenetic modification in steady, dectinn-1 activated with or without NFAT inhibiton.

2015-01-05 | E-GEOD-59998 | biostudies-arrayexpress

Expression data from Human CD40L+ Tcells

Project description:To assess the nature of CD8+CD40L+ memory Tcells, we compared the gene expression to CD8+CD40L- and CD4+ counterparts, and found similarities in expression of genes encoding cytokines. PBMCs were isolated from five healthy donors. The cells were stimulated with PMA/Ionomycin for 6 h, and subsequently sorted into the CD4+CD45RA-CD40L+, CD8+CD45RA-CD40L-, CD8+CD45RA-CD40L+ populations by FACS-sort.

2019-01-30 | E-MTAB-1497 | biostudies-arrayexpress

T Cell Receptor-Induced NF-kB Signaling and Transcriptional Activation Are Regulated by STIM1- and Orai1-Mediated Calcium Entry

Project description:T cell activation following antigen binding to the T cell receptor (TCR) involves the mobilization of intracellular calcium (Ca2+) to activate the key transcription factors NFAT and NF-ÎºB. The mechanism of NFAT activation by Ca2+ has been determined; however, the role of Ca2+ in controlling NF-ÎºB signaling is poorly understood and the source of Ca2+ required for NF-ÎºB activation is unknown. We demonstrate that TCR- but not TNF- induced NF-ÎºB signaling upstream of IÎºB kinase (IKK) activation absolutely requires the influx of extracellular Ca2+ via STIM1-dependent CRAC/Orai channels. We further show that Ca2+ influx controls phosphorylation of the NF-ÎºB protein p65 on Ser536 and that this post- translational modification controls its nuclear localization and transcriptional activation. Notably our data reveal that this role for Ca2+ is entirely separate from its upstream control of IÎºBÎ± degradation, thereby identifying a novel Ca2+- dependent distal step in TCR-induced NF-ÎºB activation. Finally, we demonstrate that this control of distal signaling occurs via Ca2+-dependent PKCk-mediated phosphorylation of p65. Thus, we establish the source of Ca2+ required for TCR induced NF-kB activation and we define a new distal Ca2+-dependent checkpoint in TCR-induced NF-kB signaling that has broad implications for the control of immune cell development and T cell functional specificity. 3 treatments were analyzed, with biological replicates for each treatment. In addition, three timepoints (1 hour, 4 hour, and 8 hour) were examined for each treatment, as well as an untreated control. In total 19 samples were analyzed

2016-01-14 | E-GEOD-76804 | biostudies-arrayexpress

BATF and IRF4 cooperate to counter exhaustion in tumour-infiltrating CAR T cells (RNA-seq)

Project description:Cooperative interactions among transcription factors are essential for gene transcription. We previously showed that NFAT and AP-1 (Fos-Jun) transcription factors cooperate to promote the effector functions of T cells, but that under conditions where it is unable to cooperate with AP-1, NFAT imposes a negative feedback programme of T cell hyporesponsiveness (“exhaustion”). Here we show that BATF and IRF4 cooperate to counter T cell exhaustion. Overexpression of Batf in CD8+ 42 T cells expressing a chimeric antigen receptor (CAR) promoted the survival and expansion of tumour-infiltrating CAR T cells, increased their production of effector cytokines, decreased their expression of inhibitory receptors and the exhaustion-associated transcription factor TOX, and led to the generation of long-lived memory T cells that controlled tumour recurrence. These responses were dependent on the BATF-IRF interaction, since cells expressing a Batf mutant unable to interact with Irf4 did not survive in tumours and did not effectively delay tumour growth. We suggest that BATF overexpression is a therapeutically viable option for improving the anti-tumour responses of CAR TILs, by skewing their phenotypes and transcriptional profiles away from exhaustion and towards increased effector function.

2021-07-13 | GSE154745 | GEO

BATF and IRF4 cooperate to counter exhaustion in tumour-infiltrating CAR T cells (ChIP-seq)

2021-07-13 | GSE154743 | GEO

BATF and IRF4 cooperate to counter exhaustion in tumour-infiltrating CAR T cells (ATAC-seq)

2021-07-13 | GSE154742 | GEO