Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

PLPP1-deficiency-mediated ferroptosis induced by PD-1 signaling impairs antitumor activity of intratumoral CD8+ T cells III.

ABSTRACT: Metabolic programming plays a crucial role in T-cell activation. Herein, we describe how phospholipid metabolism regulates CD8+ T-cell function in patients with cancer. We found that phosphatidylcholine (PC) and phosphatidyl ethanolamine (PE) levels were lower in intratumoral CD8+ T cells than in circulating CD8+ T cells. The expression of phospholipid phosphatase 1 (PLPP1), an enzyme that catalyzes PE and PC synthesis, was also downregulated in CD8+ T cells upon infiltrating tumors. Moreover, unsaturated fatty acid-mediated ferroptosis was a major factor impairing the antitumor function of PLPP1-deficient CD8+ T cells infiltrated in tumors, accompanied by enhanced reactive oxygen species production and lipid peroxidation. The activation of programmed cell death 1 (PD-1) signaling in CD8+ T cells suppressed the PLPP1 expression by increasing GATA1 binding to the promoter region of PLPP1. PLPP1 expression was upregulated after anti-PD-1 therapy. Our findings revealed therapeutic potential of enhancing PLPP1 levels to restore CD8+ T-cell function.

ORGANISM(S): Mus musculus

PROVIDER: GSE262231 | GEO | 2024/05/17

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

PLPP1-deficiency-mediated ferroptosis induced by PD-1 signaling impairs antitumor activity of intratumoral CD8+ T cells II

Project description:Metabolic programming plays a crucial role in T-cell activation. Herein, we describe how phospholipid metabolism regulates CD8+ T-cell function in patients with cancer. We found that phosphatidylcholine (PC) and phosphatidyl ethanolamine (PE) levels were lower in intratumoral CD8+ T cells than in circulating CD8+ T cells. The expression of phospholipid phosphatase 1 (PLPP1), an enzyme that catalyzes PE and PC synthesis, was also downregulated in CD8+ T cells upon infiltrating tumors. Moreover, unsaturated fatty acid-mediated ferroptosis was a major factor impairing the antitumor function of PLPP1-deficient CD8+ T cells infiltrated in tumors, accompanied by enhanced reactive oxygen species production and lipid peroxidation. The activation of programmed cell death 1 (PD-1) signaling in CD8+ T cells suppressed the PLPP1 expression by increasing GATA1 binding to the promoter region of PLPP1. PLPP1 expression was upregulated after anti-PD-1 therapy. Our findings revealed therapeutic potential of enhancing PLPP1 levels to restore CD8+ T-cell function.

2024-03-19 | GSE261644 | GEO

PLPP1-deficiency-mediated ferroptosis induced by PD-1 signaling impairs antitumor activity of intratumoral CD8+ T cells I

2024-03-19 | GSE261642 | GEO

A metabolic function for phospholipid and histone methylation

Project description:S-adenosylmethionine (SAM) is the methyl donor for biological methylation modifications that regulate protein and nucleic acid functions. Here we show that methylation of a phospholipid, phosphatidylethanolamine (PE), is the major consumer of SAM in budding yeast. The induction of phospholipid biosynthetic genes is accompanied by induction of the enzyme that hydrolyzes S-adenosylhomocysteine (SAH), a product and inhibitor of methyltransferases. Beyond its function for the synthesis of phosphatidylcholine (PC), the methylation of PE facilitates the turnover of SAM for the synthesis of cysteine and glutathione. Strikingly, cells that lack PE methylation accumulate SAM, which leads to hypermethylation of histones and the major phosphatase PP2A, dependency on cysteine, and sensitivity to oxidative stress. Without PE methylation, particular sites on histones then become methyl sinks to enable the turnover of SAM. These findings reveal an unforeseen metabolic function for phospholipid and histone methylation intrinsic to the life of a cell.

2017-03-30 | GSE84059 | GEO

The effect of ethanolamine phosphate phosphorylase knockout on hepatic gene expression

Project description:Ethanolamine phosphate phospholyase (ETNPPL) is an enzyme that irreversibly degrades phospho-ethanolamine (p-ETN), an intermediate in the Kennedy pathway of phosphatidylethanolamine (PE) biosynthesis. PE is the second most abundant phospholipid in mammalian membranes. Disturbance of hepatic phospholipid homeostasis has been linked to the development of metabolic dysfunction-associated steatotic liver disease (MASLD). We generated whole-body Etnppl knockout mice to investigate the impact of genetic deletion of Etnppl on hepatic lipid metabolism. Female Etnppl+/+ and Etnppl-/- mice were fed either a chow diet for 20 weeks and livers were harvested for lipds, proteins, and gene expression studies.

2024-11-25 | GSE271787 | GEO

Phospholipid Metabolites of the Gut Microbiota Promote Hypoxia-induced Intestinal Injury via CD1d-dependent gd T Cells

Project description:Phospholipid metabolites PE and PC are presented by intestinal epithelial CD1d to induce the proliferation of IL-17A-producing γδ T cells, which aggravates intestinal injury.

2022-04-01 | GSE199645 | GEO

Disturbed intramitochondrial phosphatidic acid transport impairs cellular stress signaling

Project description:Lipid transfer proteins of the Ups1/PRELID1 family facilitate the transport of phospholipids across the intermembrane space of mitochondria in a lipid-specific manner. Heterodimeric complexes of yeast Ups1/Mdm35 or human PRELID1/TRIAP1 shuttle phosphatidic acid (PA) synthesized in the endoplasmic reticulum (ER) to the inner membrane, where it is converted to cardiolipin (CL), the signature phospholipid of mitochondria. Loss of Ups1/PRELID1 proteins impairs the accumulation of CL and broadly affects mitochondrial structure and function. Unexpectedly and unlike yeast cells lacking the cardiolipin synthase Crd1, Ups1 deficient yeast cells exhibit glycolytic growth defects, pointing to functions of Ups1-mediated PA transfer beyond CL synthesis. Here, we show that the disturbed intramitochondrial transport of PA in ups1 cells leads to altered phospholipid composition of the ER membrane, independent of disturbances in CL synthesis. The impaired flux of PA into mitochondria is associated with the increased synthesis of phosphatidylcholine (PC) and a reduced phosphatidylethanolamine (PE)/PC ratio in the ER of ups1 cells which suppresses the unfolded protein response (UPR). Moreover, we observed inhibition of TORC1 signaling in these cells. Activation of either UPR by ER protein stress or of TORC1 signaling by disruption of its negative regulator, the SEACIT complex, increased cytosolic protein synthesis and restored glycolytic growth of ups1 cells. These results demonstrate that PA influx into mitochondria is required to preserve ER membrane homeostasis and that its disturbance is associated with impaired glycolytic growth and cellular stress signaling.

2021-01-22 | PXD022321 | Pride

Gene expression of livers from Lpcat3fl/fl and Lpcat3fl/fl Albumin-Cre mice on chow diet

Project description:The total abundance of phosphatidylcholine (PC) is known to influence lipoprotein production. However, the role of specific phospholipid species in lipid transport has been difficult to assess due to an inability to selectively manipulate membrane composition in vivo. Here we show that the LXR-regulated phospholipid remodeling enzyme lysophosphatidylcholine acyltransferase 3 (Lpcat3) is a critical determinant of membrane phospholipid composition and lipoprotein production. Mice lacking Lpcat3 in the liver show defects in lipoprotein production. The objective of generating this dataset was to analyze the effects of Lpcat3 loss of function on baseline gene expression in mouse liver. This dataset compares gene expression in Lpcat3fl/fl and Lpcat3fl/fl Albumin-Cre liver samples from 12-week old male mice that were subjected to 6 hr fasting. Each sample contains tissues from 5 mice.

2015-06-26 | E-GEOD-65352 | biostudies-arrayexpress

Gene expression of livers from Lpcat3fl/fl and Lpcat3fl/fl Albumin-Cre mice on a western diet

Project description:The total abundance of phosphatidylcholine (PC) is known to influence lipoprotein production. However, the role of specific phospholipid species in lipid transport has been difficult to assess due to an inability to selectively manipulate membrane composition in vivo. Here we show that the LXR-regulated phospholipid remodeling enzyme lysophosphatidylcholine acyltransferase 3 (Lpcat3) is a critical determinant of membrane phospholipid composition and lipoprotein production. Mice lacking Lpcat3 in the liver show defects in lipoprotein production. The objective of generating this dataset was to analyze the effects of Lpcat3 loss of function on gene expression in mouse liver with a western diet challenge.

2015-06-26 | GSE65353 | GEO

Gene expression of livers from Lpcat3fl/fl and Lpcat3fl/fl Albumin-Cre mice on chow diet

2015-06-26 | GSE65352 | GEO

Gene expression of livers from Lpcat3fl/fl and Lpcat3fl/fl Albumin-Cre mice on a western diet

Project description:The total abundance of phosphatidylcholine (PC) is known to influence lipoprotein production. However, the role of specific phospholipid species in lipid transport has been difficult to assess due to an inability to selectively manipulate membrane composition in vivo. Here we show that the LXR-regulated phospholipid remodeling enzyme lysophosphatidylcholine acyltransferase 3 (Lpcat3) is a critical determinant of membrane phospholipid composition and lipoprotein production. Mice lacking Lpcat3 in the liver show defects in lipoprotein production. The objective of generating this dataset was to analyze the effects of Lpcat3 loss of function on gene expression in mouse liver with a western diet challenge. This dataset compares gene expression in Lpcat3fl/fl and Lpcat3fl/fl Albumin-Cre liver samples from 16-week old male mice that were fed a western diet for 9 weeks since 7 weeks old. Each sample contains tissues from 5 mice.

2015-06-26 | E-GEOD-65353 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data