Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

ERYTHROID MITOCHONDRIAL RETENTION TRIGGERS MYELOID-DEPENDENT TYPE I INTERFERON IN HUMAN SLE

ABSTRACT: Using both in vitro-derived RBCs as well as RBCs isolated from SLE and CANDLE patients we were able to demonstrate that a defective proteasome activation during human erythropoiesis leads to the generation of pro-inflammatory RBCs that retain mitochondria.

ORGANISM(S): Homo sapiens

PROVIDER: GSE163073 | GEO | 2021/08/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Erythroid mitochondrial retention triggers myeloid-dependent type I interferon in human SLE.

Project description:Emerging evidence supports that mitochondrial dysfunction contributes to systemic lupus erythematosus (SLE) pathogenesis. Here we show that programmed mitochondrial removal, a hallmark of mammalian erythropoiesis, is defective in SLE. Specifically, we demonstrate that during human erythroid cell maturation, a hypoxia-inducible factor (HIF)-mediated metabolic switch is responsible for the activation of the ubiquitin-proteasome system (UPS), which precedes and is necessary for the autophagic removal of mitochondria. A defect in this pathway leads to accumulation of red blood cells (RBCs) carrying mitochondria (Mito+ RBCs) in SLE patients and in correlation with disease activity. Antibody-mediated internalization of Mito+ RBCs induces type I interferon (IFN) production through activation of cGAS in macrophages. Accordingly, SLE patients carrying both Mito+ RBCs and opsonizing antibodies display the highest levels of blood IFN-stimulated gene (ISG) signatures, a distinctive feature of SLE.

| S-EPMC8380737 | biostudies-literature

ERYTHROID MITOCHONDRIAL RETENTION TRIGGERS MYELOID-DEPENDENT TYPE I INTERFERON IN HUMAN SLE

Project description:ERYTHROID MITOCHONDRIAL RETENTION TRIGGERS MYELOID-DEPENDENT TYPE I INTERFERON IN HUMAN SLE

| PRJNA684605 | ENA

Type I Interferon promotes MxA-dependent IL-1b release in SLE monocytes

Project description:Systemic lupus erythematosus (SLE) is characterized by upregulation of Type Ι Interferon (IFN) and widespread inflammation. However, blocking the IFN pathway benefits a fraction of patients, pointing to additional pathogenic players. Here we describe monocytes (Mo) undergoing erythrophagocytosis and co-expressing IFN-inducible genes (ISGs) and interleukin-1b (IL-1b) in patients with active disease. This phenotype is recapitulated in vitro upon internalization of red blood cells carrying mitochondria (Mito+ RBCs), a feature of SLE. While ISG expression requires the interaction between Mito+ RBC-derived mitochondrial DNA (mtDNA) and cGAS, the production of IL-1b entails Mito+ RBC-derived mitochondrial RNA (mtRNA) triggering RIG-I-like receptor (RLR) activation. This leads to the cytosolic release of Mo-derived mtDNA and activation of the NLRP3 inflammasome. Importantly, the Type I IFN-inducible protein myxovirus resistant protein 1 (MxA) enables IL-1b release by routing this cytokine into a trans-Golgi network (TGN)-mediated unconventional secretory pathway. As Type I IFN and IL-1b are thought to counter-regulate each other, our study highlights an unprecedented synergy between these two cytokine pathways in SLE.

2024-10-07 | GSE211361 | GEO

Transcriptional profiles of pediatric SLE neutrophils and Healthy neutrophils cultured with SLE sera or Interferon

Project description:Mature neutrophis were freshly isolated from blood of pediatric systemic lupus erythematosus (SLE) patients and healthy donors. Illumina microarray was used to assess transcriptional changes between SLE group and Control group. To uderstand further the gene expression difference between SLE and healthy neutrofils, neutrophils from healthy donors were cultured with autologous sera, SLE sera or Interferon and microarray data was used to compare with fresh SLE neutrophils. (Expt 1) Neutrophils from 21 SLE samples (19 patients) and 12 healthy donors were isolated, and extracted RNAs were used generate microarray data. (Expt 2) Neutrophils isolated from 2 healthy children (not used in the first experiment) were cultured with autologous sera (control), Interferon alpha (100U and 1000U), and 4 SLE sera and 6 SLE sera for 6 hours and RNAs were extract for microarray experiment.

2011-03-10 | E-GEOD-27427 | biostudies-arrayexpress

Transcriptional profiles of pediatric SLE neutrophils and Healthy neutrophils cultured with SLE sera or Interferon

2011-03-10 | GSE27427 | GEO

Activation of the Interferon Pathway is Dependent upon Autoantibodies in African-American SLE Patients, but not in European-American SLE Patients

Project description:Systemic lupus erythematosus (SLE) is a heterogeneous disease which leads to different levels of serum autoantibodies to RNA-binding proteins (anti-RBP) and interferon-Î± (IFN-Î±), which plays an important pathogenic role in SLE, between European-American (EA) and African-American (AA) patients. We aimed to explore how IFN-related gene expression pathways differ in patients according to their ancestry and anti-RBP profile Whole blood from 33 female SLE patients and 16 matched controls from EA and AA ancestral backgrounds was analyzed through Affymetrix Gene 1.0 ST gene expression arrays and the data were further studied through Ingenuity Pathways Analysis for canonical pathway comparison. An independent replication cohort of more than 100 SLE patient samples and 30 controls was used to test the hypotheses generated by the microarray data, using qPCR to quantify gene expression.

2013-11-15 | E-GEOD-50635 | biostudies-arrayexpress

Modular repertoire analyses identify dynamic type I and type II interferon transcriptional signatures in adult SLE patients

Project description:Gene expression profiling (compared to healthy controls) to identify patients with active SLE disease and patients with quiescent disease 157 “SLE” and 20 “Healthy controls of SLE were followed up for up to 3 years. Clinical assessment, current treatment, laboratory results and SLEDAI score were collected at each visit (V1, V2...). SLE patients are compared to control groups.

2014-04-01 | E-GEOD-49454 | biostudies-arrayexpress

Activation of the Interferon Pathway is Dependent upon Autoantibodies in African-American SLE Patients, but not in European-American SLE Patients

2013-11-15 | GSE50635 | GEO

LC-MS of PBMC in SLE and healthy control

Project description:Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease that displays a significant gender difference in terms of incidence and severity. However, the underlying mechanisms accounting for sexual dimorphism remain unclear. To reveal the heterogeneity in the pathogenesis of SLE between male and female patients. PBMC were collected from 15 patients with SLE (7 males, 8 females) and 15 age-matched healthy controls (7 males, 8 females) for proteomic analysis. Enrichment analysis of proteomic data revealed that type I interferon signaling and neutrophil activation networks mapped to both male and female SLE, while male SLE has a higher level of neutrophil activation compared with female SLE. Our findings define gender heterogeneity in the pathogenesis of SLE and may facilitate the development of gender-specific treatments.

2022-08-12 | PXD033144 | Pride

Leukocyte subset-specific type 1 interferon signatures in SLE and other immune-mediated diseases.

Project description:Objectives Type 1 interferons (IFN-I) are implicated in the pathogenesis of systemic lupus erythematosus (SLE), but most studies have only reported the effect of IFN-I on mixed cell populations. We aimed to define modules of IFN-I associated genes in purified leukocyte populations and use these as a basis for a detailed comparative analysis. Methods CD4+ and CD8+ T-cells, monocytes and neutrophils were purified from patients with SLE, other immune-mediated diseases and healthy volunteers (HV)and gene expression determined by microarray. Modules of IFN-I associated genes were defined using weighted gene coexpression network analysis. The composition and expression of these modules was analysed. Results 1,150 of 1,288 IFN-I associated genes were specific to myeloid subsets, compared with 11 genes unique to T-cells. IFN-I genes were more highly expressed in myeloid subsets compared to T-cells. A subset of neutrophil samples from HV and conditions not classically associated with IFN-I signatures displayed increased IFN-I gene expression, whereas upregulation of IFN-I associated genes in T-cells was restricted to SLE. Conclusions Given the broad upregulation of IFN-I genes in neutrophils including in some HV, investigators reporting IFN-I signatures on the basis of whole blood samples should be cautious about interpreting this as evidence of bona fide IFN-I mediated pathology. Instead, specific upregulation of IFN-I associated genes in T-cells may be a useful biomarker and a further mechanism by which elevated IFN-I contributes to autoimmunity in SLE.

2016-06-01 | E-MTAB-2713 | 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