Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A bioactive mammalian disaccharide associated with autoimmunity activates a STING-TBK1-dependent immune response

ABSTRACT: DNase III, also known as TREX1, is a 314 amino acid endoplasmic reticulum (ER) tail-anchored 3’ exonuclease where the N-terminal region contains the DNase domain and the C-terminal end controls TREX1 localization to the surface of the ER. Disease mutations in the C-terminal region alters TREX1 ability to interact with the oligosaccharyltransferase (OST) subunits Ribophorin 1 (RPN1) and DDOST leading to rapid hydrolysis of lipid-linked oligosaccharides (LLOs) into bioactive free oligosaccharides (fOS) in a switch-like manner. Bioassay-guided fractionation of the fOS pool revealed that the structure responsible for the bioactivity is a mannose (Man) b1-4 N-acetylglucosamine (GlcNAc) disaccharide. The bioactive disaccharide is produced from OST’s hydrolyzed LLOs in the cytoplasm and activates a STING-TBK1 dependent immune signal that leads to the upregulation of interferon-stimulated genes (ISGs) and chemokine genes.

ORGANISM(S): Mus musculus

PROVIDER: GSE129677 | GEO | 2019/04/16

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Identification of gene expression patterns in spleen of TREX1-mutated mice

Project description:Investigating gene expression patterns in mice with conditional expression of the most common RVCL mutation, V235fs, and another mice expressing a conditional C-terminal mutation, D272fs, associated with a case of human SLE. Mutations at the N-terminus affecting TREX1 DNase activity are associated with autoimmune and inflammatory conditions such as Aicardi-Goutières syndrome (AGS). Mutations in the C-terminus of TREX1 cause loss of localization to the ER and dysregulation of oligosacchryltransferase (OST) activity, and are associated with retinal vasculopathy with cerebral leukodystrophy (RVCL) and in some cases with systemic lupus erythematosus (SLE).

2018-03-15 | GSE96687 | GEO

Oligosaccharyl transferase that maintains ER homeostasis enhances immunity via up-regulating p38 MAP kinase signaling in C. elegans

Project description:Oligosaccharyl transferase (OST) protein complex mediates the N-linked glycosylation of substrate proteins in the endoplasmic reticulum (ER), which regulates stability, activity and localization of its substrates. Although many OST substrate proteins have been identified, the physiological role of OST complex remains incompletely understood. Here, we show that OST complex in C. elegans is crucial for ER protein homeostasis and enhances resistance to pathogenic bacteria, Pseudomonas aeruginosa (PA14), via immune-regulatory PMK-1/p38 MAP kinase.

2020-01-30 | GSE134687 | GEO

shRNA TMEM258 knockdown in HeLa

Project description:TMEM258 is associated with the OST complex. Loss of TMEM258 induces ER stress.

2016-11-05 | GSE89542 | GEO

Transcription profiling of rat colon from animals fed cellulose vs FOS diets and infected with Salmonella

Project description:To increase our knowledge of the effects of Fructo oligosaccharides (FOS) on Salmonella infection in fats, a controlle rat infection study was performed. Two groups of 12 rats were adapted for 14 days to a cellulose diet and one group of 12 rats to a FOS diet. One cellulose-fed group and the FOS-fed group were infected with Salmonella. Two days post infection mRNA was collected from the mucosa of the colon and changes in gene expression were assessed using an Agilent rat whole genome microarray (G4131A Agilent Technologies). Results indicate that Salmonella affects colonic mucosal gene expression, which is further enhanded by dietary FOS. Experiment Overall Design: In the present study, large-scale gene expression analysis was performed to reveal whether Salmonella induced changes of colonic mucosal gene expression in rats. Furthermore, we compared the colonic gene expression changes of infected rats fed a diet supplemented with Fructo oligosaccharides (FOS) or cellulose as control. Two groups of Wistar rats (n=12) were adapted for 14 days to a cellulose diet and one group (n=12) to a FOS diet. One cellulose-fed group and the FOS-fed group were infected with Salmonella. RNA was isolated from colonic mucosal scrapings. mRNA samples of 12 rats per group were pooled. Each group-sample was hybridised in duplicate on Agilent rat whole genome microarrays containing 44290 60-mer spots.

2008-06-15 | E-GEOD-7472 | biostudies-arrayexpress

Transcription profiling of rat colon after dietary treatment with fructo oligosaccharides

Project description:To increase our knowledge of the effects of Fructo oligosaccharides (FOS) on the intestinal barrier function in rats, a controlled rat infection study was performed. Two groups of rats were adapted to a diet with or without FOS. mRNA was collected from the mucosa of the colon and changes in gene expression were assessed using an agilent rat whole genome microarray (G4131A Agilent Technologies). Results indicate that dietary FOS influences energy metabolism, which will most likely play a role in the effects of FOS on the intestinal barrier. Experiment Overall Design: In the present study, large-scale gene expression analysis was performed to reveal mechanistic details of FOS induced gene expression in vivo in the colon mucosa. Wistar rats were adapted to diets with or without FOS for 14 days. RNA was isolated from colonic mucosal scrapings. Agilent rat whole genome microarray containing 44290 60-mer spots, were used to study FOS induced gene expression changes in order to better understand the FOS induced effects on the intestinal barrier of rats.

2008-06-14 | E-GEOD-5943 | biostudies-arrayexpress

Colonic gene expression upon dietary treatment

2007-12-01 | GSE5943 | GEO

TREX1 is required for microglial cholesterol homeostasis and subsequent oligodendrocyte maturation during brain development [bulk RNA-seq]

Project description:Three Prime Repair Exonuclease 1 (TREX1) gene mutations have been associated with Aicardi-Goutières Syndrome (AGS) – a rare, severe pediatric autoimmune disorder that primarily affects the brain and has a poorly understood etiology. Microglia are brain-resident macrophages indispensable for brain development and implicated in multiple neuroinflammatory diseases. However, the role of TREX1 – a DNase that cleaves cytosolic nucleic acids, preventing viral- and autoimmune-related inflammatory responses – in microglia biology remains to be elucidated. Here, we leverage a model of human embryonic stem cell (hESC)-derived engineered microglia-like cells, bulk and single-cell transcriptomics, optical and transmission electron microscopy, and three-month-old assembloids composed of microglia and regionalized neural organoids to interrogate TREX1 functions in human microglia. Our analyses suggest that TREX1 influences cholesterol metabolism, leading to an active microglial morphology with increased phagocytosis in the absence of TREX1. Notably, regulating cholesterol metabolism with an HMG-CoA reductase inhibitor, FDA-approved atorvastatin, rescues these microglial phenotypes. Functionally, TREX1-deficient microglia selectively affect oligodendrocyte maturation and myelination in assembloids. Together, these results suggest routes for therapeutic intervention in pathologies such as AGS based on microglia-specific molecular and cellular mechanisms.

2023-11-23 | GSE216702 | GEO

Transcription profiling of rat cecum mucosa upon dietary treatment with fructo oligosaccharides

Project description:To increase our knowledge of the effects of Fructo oligosaccharides (FOS) on the intestinal barrier function in rats, a controlled rat infection study was performed. Two groups of rats (n=12 per group) were adapted to a diet with or without FOS. mRNA was collected from the mucosa of the cecum and changes in gene expression were assessed using an agilent rat whole genome microarray (G4131A Agilent Technologies). Results indicate that dietary FOS influences immune response and wound healing mechanisms, which will most likely affect the intestinal barrier. Experiment Overall Design: In the present study, large-scale gene expression analysis was performed to reveal mechanistic details of FOS induced gene expression in vivo in the cecum mucosa. Wistar rats were adapted to diets with (n=12) or without FOS (n=12) for 14 days. RNA was isolated from cecum mucosal scrapings, two RNA samples from the control group were ecluded based on poor quality of RNA. Agilent rat whole genome microarray containing 44290 60-mer spots, were used to study FOS induced gene expression changes in order to better understand the FOS induced effects on the intestinal barrier of rats.

2008-06-18 | E-GEOD-8587 | biostudies-arrayexpress

Gene expression changes in cecum mucosa upon dietary treatment

2007-12-31 | GSE8587 | GEO

open stomata2-Open stomata 2 mutant

Project description:af73_ost2 - open stomata2 - transcription profiling of the open stomata 2 mutant hypersensitive to drought - Ler vs OST (Open STomata mutant), Ler drought vs OST drought Ler vs Ler drought OST vs OST drought Keywords: wt vs mutant comparison

2007-06-20 | GSE7982 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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