Prostaglandin E2 (PGE2) Enhances Aged Hematopoietic Stem Cell Function
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA729494 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The purpose of this RNA sequencing dataset was to analyze transcriptional signaling in young and aged murine hematopoietic stem cells when pulsed ex vivo with dimethyl (dm)PGE2.
2021-05-13 | GSE174346 | GEO
Project description:Tumour immune escape is a major factor contributing to cancer progression and unresponsiveness to cancer therapies. Tumours can produce prostaglandin E2 (PGE2), an inflammatory mediator that directly acts on NK cells to inhibit anti-tumour immunity. However, it is unclear precisely how PGE2 influences NK cell tumour-restraining functions. Here, we investigated how treatment with PGE2 over 24 hours affects gene expression in human NK cells.
2023-11-28 | E-MTAB-13106 | biostudies-arrayexpress
Project description:Prostaglandins are involved in maintaining tissue integrity under homeostatic conditions. However, in chronic inflammation and cancer prostaglandins have been linked to immune deviation including strong suppression of effector T-cell function. Yet, the molecular mechanisms underlyingimmunosuppression and the cell types involved are only purely understood. Here, we show for the first time that Treg cells are the critical cellular component exerting immunosuppressive effects in prostaglandin E2 (PGE2)-rich environments. Hydroxyprostaglandin dehydrogenase (HPGD), which catabolizes PGE2 into immunosuppressive metabolites, is the critical molecular link between prostaglandin accumulation, increased Treg-cell function and avoidance of tissue destruction.
2019-10-07 | GSE62579 | GEO
Project description:Recognition of foreign antigens by B cell receptor (BCR) on mature B cells leads to their clonal expansion, which is critically important for the effective host defence of the organism. However, excessive antigenic responses or reaction of B cells against bodyâs own components frequently lead to diverse immune diseases, such as B-cell lymphoma or autoimmunity, that often affect humans. Identification of genes that restrain uncontrolled proliferation of B cells is therefore an important goal towards understanding the origin of such diseases. Here we identify Ptger4 as a negative feedback regulator of B-cell proliferation in response to BCR triggering, and show that its encoded EP4 receptor is a principal molecule conveying the growth-suppressive effect of prostaglandin E2 (PGE2). In controlled in vitro assays, Ptger4-/- B cells showed augmented proliferative response and increased expression of activating genes upon BCR stimulation. Stable knock-down of Ptger4 in B-cell lymphoma markedly accelerated tumour spread in mice, while Ptger4 overexpression yielded significant protection. Lack of Ptger4 rendered mouse B cells completely resistant to proliferation arrest signalled by PGE2, and we find by transcriptional profiling that intrinsic activity of Ptger4 and PGE2-EP4 signalling target a similar set of activating genes. We further show that Ptger4 inhibits mouse B-cell activation in vivo and find it significantly downregulated in human B-cell lymphoma. Our results demonstrate that Ptger4 functions in B cells as a candidate tumour suppressor whose activity is regulated by the presence of PGE2 in the microenvironment. These findings suggest that targeting EP4 receptor for prostaglandin may present a novel strategy for treatment of B-cell diseases. Keywords: time course, cell type comparison, compound treatment design, microarray experiment record B cells were extracted from spleen of Ptger4+/+ and Ptger4-/- mice, and incubated in vitro for the indicated period with or without anti-IgM (Fab')2 antibody fragments and co-treated with or without PGE2. Total RNA was extracted, amplified, labelled with Cy3 or Cy5, and hybridized to mouse 24k oligo-arrays using a dye-swap strategy.
2008-12-14 | E-GEOD-9847 | biostudies-arrayexpress
Project description:Prostaglandin E2 (PGE2) is overexpressed in many tumors and plays an important role in suppressing T-cell function. In this study, we investigated the effect of PGE2 in human T-cells. Importantly, PGE2 caused profound transcriptomic changes both in unstimulated and exhausted T-cells with many genes and pathways altered including T-cell lipid metabolism. Our study suggests that PGE2-induced metabolic reprogramming is detrimental to dysfunctional T-cells and TIL, and its manipulation could be used to dampen the immunosuppressive effects of PGE2.
2024-03-08 | GSE227316 | GEO
Project description:total RNA from mouse (male c57BL/6) spleen labeled with Cy3 vs total RNA from mouse (male c57BL/6) B cells treated with Prostaglandin E2 labeled with Cy5- time course with repeats Keywords: ordered
2003-04-14 | GSE395 | GEO
Project description:Recognition of foreign antigens by B cell receptor (BCR) on mature B cells leads to their clonal expansion, which is critically important for the effective host defence of the organism. However, excessive antigenic responses or reaction of B cells against body’s own components frequently lead to diverse immune diseases, such as B-cell lymphoma or autoimmunity, that often affect humans. Identification of genes that restrain uncontrolled proliferation of B cells is therefore an important goal towards understanding the origin of such diseases. Here we identify Ptger4 as a negative feedback regulator of B-cell proliferation in response to BCR triggering, and show that its encoded EP4 receptor is a principal molecule conveying the growth-suppressive effect of prostaglandin E2 (PGE2). In controlled in vitro assays, Ptger4-/- B cells showed augmented proliferative response and increased expression of activating genes upon BCR stimulation. Stable knock-down of Ptger4 in B-cell lymphoma markedly accelerated tumour spread in mice, while Ptger4 overexpression yielded significant protection. Lack of Ptger4 rendered mouse B cells completely resistant to proliferation arrest signalled by PGE2, and we find by transcriptional profiling that intrinsic activity of Ptger4 and PGE2-EP4 signalling target a similar set of activating genes. We further show that Ptger4 inhibits mouse B-cell activation in vivo and find it significantly downregulated in human B-cell lymphoma. Our results demonstrate that Ptger4 functions in B cells as a candidate tumour suppressor whose activity is regulated by the presence of PGE2 in the microenvironment. These findings suggest that targeting EP4 receptor for prostaglandin may present a novel strategy for treatment of B-cell diseases. Keywords: time course, cell type comparison, compound treatment design, microarray experiment record
2008-12-15 | GSE9847 | GEO
Project description:Myeloid-derived suppressor cells (MDSC) include immature monocytic (M-MDSC) and granulocytic (PMN-MDSC) cells that share the ability to suppress adaptive immunity and hinder the effectiveness of anti-cancer treatments. Of note, in response to interferon-γ (IFNγ) M-MDSC release the tumor-promoting and immunosuppressive molecule nitric oxide (NO), whereas macrophages largely express anti-tumor properties. Investigating these opposing activities, we found that tumor-derived prostaglandin E2 (PGE2) induces nuclear accumulation of p50 NF-κB in M-MDSC, diverting their response to IFNγ towards NO-mediated immunosuppression and reducing TNFα expression. At the genome level, p50 NF-κB promoted binding of STAT1 to regulatory regions of selected IFNγ-dependent genes, including inducible nitric oxide synthase (Nos2). In agreement, ablation of p50 as well as pharmacological inhibition of either the PGE2 receptor EP2 or NO production reprogrammed M-MDSC towards a NOS2low/TNFαhigh phenotype, restoring the in vivo antitumor activity of IFNγ. Our results indicate that inhibition of the PGE2/p50/NO axis prevents MDSC suppressive functions and restores the efficacy of anticancer immunotherapy.
2020-05-15 | GSE84468 | GEO
Project description:Immune cells must adapt to different environments during an immune response. We studied the adaptation of CD8+ T cells to the intestinal microenvironment and how this process shapes tissue resident CD8+ T cells (TRM) in the gut. CD8+ T cells progressively remodel their transcriptome and surface phenotype as they acquire gut residency, and downregulate mitochondrial gene expression. Human and mouse gut-resident CD8+ T cells have reduced mitochondrial mass, but maintain a viable energy balance to sustain function. We found that the intestinal microenvironment is rich in prostaglandin E2 (PGE2), which drives mitochondrial depolarization in CD8+ T cells. Consequently, they engage autophagy to clear depolarized mitochondria, and enhance glutathione synthesis to scavenge reactive oxygen species (ROS). Impairing PGE2 sensing promotes TRM accumulation, while tampering with autophagy and glutathione negatively impacts the TRM pool. Thus, a PGE2-autophagy-glutathione axis defines the metabolic adaptation of CD8+ T cells to the intestinal microenvironment, to ultimately influence the TRM pool.
2023-11-27 | GSE200567 | GEO
Project description:Immune cells must adapt to different environments during an immune response. We studied the adaptation of CD8+ T cells to the intestinal microenvironment and how this process shapes tissue resident CD8+ T cells (TRM) in the gut. CD8+ T cells progressively remodel their transcriptome and surface phenotype as they acquire gut residency, and downregulate mitochondrial gene expression. Human and mouse gut-resident CD8+ T cells have reduced mitochondrial mass, but maintain a viable energy balance to sustain function. We found that the intestinal microenvironment is rich in prostaglandin E2 (PGE2), which drives mitochondrial depolarization in CD8+ T cells. Consequently, they engage autophagy to clear depolarized mitochondria, and enhance glutathione synthesis to scavenge reactive oxygen species (ROS). Impairing PGE2 sensing promotes TRM accumulation, while tampering with autophagy and glutathione negatively impacts the TRM pool. Thus, a PGE2-autophagy-glutathione axis defines the metabolic adaptation of CD8+ T cells to the intestinal microenvironment, to ultimately influence the TRM pool.
2023-11-27 | GSE200566 | GEO