Altered transcriptional programming in Nur77-GFPhi naïve CD8 T cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA926346 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR23186773_1.fastq.gz | Fastqsanger.gz | |||
| SRR23186773_2.fastq.gz | Fastqsanger.gz | |||
| SRR23186774_1.fastq.gz | Fastqsanger.gz | |||
| SRR23186774_2.fastq.gz | Fastqsanger.gz | |||
| SRR23186775_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 12 |
Similar Datasets
Project description:Naive T cells experience accumulation of TCR signaling in response to self-antigens in the steady state. However, how these signals influence the responsiveness of naive CD8+ T cells to subsequent agonist TCR stimulation remains incompletely understood. We investigated how naive CD8+ T cells that experienced relatively low or high levels of TCR signaling in response to self-antigens respond to stimulation with foreign antigens. A transcriptional reporter of Nr4a1 (Nur77-GFP) revealed substantial heterogeneity of the amount of TCR signaling naive CD8+ T cells accumulate in the steady state. To further understand the impact of differential TCR signaling on CD8 T cells we performed RNA-seq on naive Nur77-GFPhi and lo populations.
2023-03-02 | GSE223457 | GEO
Project description:Cellular programming of naïve T cells, in contrast to activated T cells, can enhance the efficacy of adoptive T cell therapy. The differentiation of naïve cells into memory T cells impairs adoptive immunotherapy. Most current strategies for ex vivo engineering of T cells require pre-activation of T cells, with CD3/CD28 crosslinking antibodies or cytokines, prior to the delivery of genetic material, and therefore T cells lose the naïve state. Here, using a cationic polymer-functionalized nanowire platform, we pre-programmed the fate of primary, naïve CD8+ T cells to achieve the therapeutic response in vivo. We demonstrate the delivery of single versus multiple microRNAs (miRNAs) to primary naïve mouse and human CD8+ T cells without pre-activation, allowing for T cell programming in user-specific ways, as well as delivery of large, whole lentiviral particles with potential for long-term integration. Because CD8 T cell differentiation is a continuous process where fate decisions require the interplay of multiple miRNAs, we demonstrate how a combination of deletion and overexpression of miR-29 and miR-130 impact ex vivo T cell differentiation fate from the naïve state. The programming of CD8+ T cells using nanowire-delivered co-delivery of miRNAs resulted in the modulation of T cell fitness by altering T cell proliferation, phenotypic and transcriptional regulation, and secretion of effector molecules. Importantly, the in vivo adoptive transfer of murine CD8+ T cells programmed through nanowire-mediated dual delivery of miRNAs provided enhanced immune protection against different types of intracellular pathogens (influenza, Listeria monocytogenes). Nanowires open up therapeutic possibilities for adoptive T cell transfers where the amounts of effector differentiation in CD8+ T cells can be fine-tuned to achieve the therapeutic response in vivo.
2024-04-03 | GSE255468 | GEO
Project description:Naïve CD44low CD25low CD8+ T cells from Bcl11bF/F/dLck-iCre and wild type mice at steady state were sorted at 90% purity, RNA was extracted and profile for mRNA expression to identify mRNAs differentially expressed in Bcl11b-/- naïve CD8+ T cells versus wild type. Naïve CD44low CD25low CD8+ T cells purified from Bcl11bF/F/dLck-iCre and wild type mice and investigated for mRNA expression
2014-04-22 | E-GEOD-56925 | biostudies-arrayexpress
Project description:CD8 T cells play a central role in antiviral immunity. Type I interferons are among the earliest responders after virus exposure and can cause extensive reprogramming and antigen-independent bystander activation of CD8 T cells. Although bystander activation of pre-existing memory CD8 T cells is known to play an important role in host defense and immunopathology, its impact on naïve CD8 T cells remains underappreciated. Here we report that exposure to reovirus, both in vitro or in vivo, promotes bystander activation of naïve CD8 T cells within 24 hours and that this distinct subtype of CD8 T cell displays an innate, antiviral, type I interferon sensitized signature. The induction of bystander naïve CD8 T cells is STAT1 dependent and regulated through nicotinamide phosphoribosyl transferase (NAMPT)-mediated enzymatic actions within NAD+ salvage metabolic biosynthesis. These findings identify a novel aspect of CD8 T cell activation following virus infection with implications for human health and physiology.
2023-01-30 | PXD039614 | Pride
Project description:The presence of B cells is essential for the formation of CD8 T cell memory after infection and vaccination. In this study, we investigated whether B cells influence the programming of naïve CD8 T cells prior to their involvement in an immune response. RNA sequencing indicated that B cells are necessary for sustaining the FOXO1-controlled transcriptional program, which is critical for their homeostasis. Without an appropriate B cell repertoire, mouse naïve CD8 T cells exhibit a terminal, effector-skewed phenotype, which significantly impacts their response to vaccination. A similar effector-skewed phenotype with reduced FOXO1 expression was observed in naïve CD8 T cells from human patients undergoing B cell-depleting therapies. Furthermore, we show that patients without B cells have a defect in generating long-lived CD8 T cell memory following COVID vaccination. In summary, we demonstrate that B cells promote the quiescence of naïve CD8 T cells, poising them to become memory cells upon vaccination.
2025-04-01 | GSE263132 | GEO
Project description:Human Naïve-like CD8 T cells induced by the Yellow Fever Vaccine 17D were compared to the conventional subsets in total CD8 T cells Samples originate from peripheral blood mononuclear cells (PBMC) from 8 different donors vaccinated with the YF-17D vaccine 1'000 cells from various CD8 T cells subsets were purified by flow cytometry, from 8 vaccinees (donors d1 to d8); the subsets (cell types) include: A2/NS4b tetramer positive CCR7+ CD45RA+ CD8 T cells (A2_NS4b Naïve-like), Total Naive (CCR7+ CD45RA+), Total Tscm (CCR7+ CD45RA+ CD58+ CD95+), Total CM (CCR7+ CD45RA-) and Total Effectors (CCR7 negative).
2015-04-08 | E-GEOD-65804 | biostudies-arrayexpress
Project description:Macrophages exhibit remarkable plasticity in their morphology and mechanics, enabling them to adapt and execute essential inflammatory functions, such as navigating through inflamed tissue and pathogen engulfment. However, the precise regulatory mechanisms governing these dynamic changes in macrophage mechanics during inflammation remain poorly understood. Although the involvement of nuclear receptor Nur77 in macrophage inflammation has been extensively investigated, its potential correlation with cellular mechanics has not been investigated. In this study, we employ cytoskeletal imaging, single-cell acoustic force spectroscopy (AFS), migration and phagocytosis experiments, and RNA-sequencing analysis on bone marrow-derived macrophages (BMDMs) to compare wild-type (WT) and Nur77-deficient (Nur77-KO) cells. Our findings reveal that Nur77-KO BMDMs exhibit changes to their actin networks compared to WT BMDMs, which is associated with a stiffer and more rigid phenotype. Subsequent in-vitro experiments validated our observations, showcasing that Nur77 deficiency leads to enhanced migration, reduced adhesion, and increased phagocytic activity. The transcriptomics data confirmed altered mechanics-related pathways in Nur77-deficient macrophage that are accompanied by a robust pro-inflammatory phenotype. Utilizing previously obtained ChIP-data, we revealed that Nur77 directly targets differentially expressed genes associated with cellular mechanics. In conclusion, while Nur77 is recognized for its role in reducing inflammation of macrophages by inhibiting the expression of pro-inflammatory genes, our study identifies a novel regulatory mechanism where Nur77 governs macrophage inflammation through the modulation of expression of genes involved in cellular mechanics.
2024-08-02 | GSE253423 | GEO
Project description:Phosphatidylinositol-3-kinase p110 delta (PI3Kp110δ) is pivotal for CD8+ T cell immune responses. To inform how PI3Kp110δ regulates CD8+ T cells, the current study focuses on PI3Kp110δ controlled transcriptional programs and reveals how PI3Kp110δ selectively induces and represses expression of key genes that create a cytotoxic T cell (CTL). The data identify differences in PI3Kp110δ regulated transcriptional programs between naïve and cytotoxic T cells including differential control of cytolytic effector molecules, costimulatory receptors and the critical inhibitory receptors CTLA4 and SLAMF6. However, common to both naïve and effector cells is PI3Kp110δ control of the production of chemokines and cytokines that orchestrate communication between the adaptive and innate immune system. The study provides a comprehensive resource for understanding how PI3Kp110δ uses multiple mechanisms dependent on Protein Kinase B/AKT, FOXO1 dependent and independent mechanisms and mitogen-activated protein kinases (MAPK) to direct CD8+ T cell fate.
2021-06-14 | PXD025046 | Pride
Project description:Phosphatidylinositol-3-kinase p110 delta (PI3Kp110δ) is pivotal for CD8+ T cell immune responses. To inform how PI3Kp110δ regulates CD8+ T cells, the current study focuses on PI3Kp110δ controlled transcriptional programs and reveals how PI3Kp110δ selectively induces and represses expression of key genes that create a cytotoxic T cell (CTL). The data identify differences in PI3Kp110δ regulated transcriptional programs between naïve and cytotoxic T cells including differential control of cytolytic effector molecules, costimulatory receptors and the critical inhibitory receptors CTLA4 and SLAMF6. However, common to both naïve and effector cells is PI3Kp110δ control of the production of chemokines and cytokines that orchestrate communication between the adaptive and innate immune system. The study provides a comprehensive resource for understanding how PI3Kp110δ uses multiple mechanisms dependent on Protein Kinase B/AKT, FOXO1 dependent and independent mechanisms and mitogen-activated protein kinases (MAPK) to direct CD8+ T cell fate.
2021-06-14 | PXD025061 | Pride
Project description:We isolated total RNA from gastrocnemius muscle of wildtype and muscle-specific Nur77 overexpressing transgenic mice to identify Nur77-mediated changes in gene expression. Findings confirmed changes in genes involved in carbohydrate metabolism and muscle development. 2 replicate Illumina Single Color Mouse WG-6_V2_0 chips were used. 6 wildtype and 6 transgenic mice overexpressing Nur77 in skeletal muscle were used. RNA was isolated by Trizol and further purified through RNEasy column. RNA from 2 mice were pooled, for a total of 6 samples -- 3 wildtype and 3 transgenic. The same samples were split into two technical replicate chips. Each chip contains 3 wildtype and 3 transgenic samples.
2015-02-04 | E-GEOD-65585 | biostudies-arrayexpress