Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Human lupus netting neutrophils induce endothelial damage, infiltrate tissues and expose immunostimulatory molecules

ABSTRACT: Our group has proposed that low-density granulocytes (LDGs) play an important role in lupus pathogenesis, as they can damage endothelial cells and synthesize increased levels of proinflammatory cytokines and type I interferons. LDGs have a heightened capacity to synthesize neutrophil extracellular traps (NETs). NETs from LDGs display increased levels of bactericidal and immunostimulatory proteins, such as the cathelicidin LL37 and externalize double-stranded DNA (dsDNA). Lupus netting LDGs have increased capacity to kill endothelial cells and expose IL-17. Through NETosis, lupus neutrophils stimulate plasmacytoid DCs to synthesize IFN-α. Our results further expand the potential pathogenic role of aberrant lupus neutrophils through a NET-mediated effect. We used microarrays to analyze the gene expression of neutrophils in healthy and lupus patients, and of low-density granulocytes in lupus patients.

ORGANISM(S): Homo sapiens

PROVIDER: GSE26975 | GEO | 2011/06/22

SECONDARY ACCESSION(S): PRJNA135917

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Human lupus netting neutrophils induce endothelial damage, infiltrate tissues and expose immunostimulatory molecules

Project description:Our group has proposed that low-density granulocytes (LDGs) play an important role in lupus pathogenesis, as they can damage endothelial cells and synthesize increased levels of proinflammatory cytokines and type I interferons. LDGs have a heightened capacity to synthesize neutrophil extracellular traps (NETs). NETs from LDGs display increased levels of bactericidal and immunostimulatory proteins, such as the cathelicidin LL37 and externalize double-stranded DNA (dsDNA). Lupus netting LDGs have increased capacity to kill endothelial cells and expose IL-17. Through NETosis, lupus neutrophils stimulate plasmacytoid DCs to synthesize IFN-?. Our results further expand the potential pathogenic role of aberrant lupus neutrophils through a NET-mediated effect. We used microarrays to analyze the gene expression of neutrophils in healthy and lupus patients, and of low-density granulocytes in lupus patients. Human neutrophils and LDGs were isolated from PBMCs. RNA from healthy neutrophils, lupus neutrophils and lupus LDGs was extracted and processed for hybridization on Affymetrix microarrays.

2011-06-22 | E-GEOD-26975 | biostudies-arrayexpress

RNA externalized by neutrophil extracellular traps promotes inflammatory pathways in endothelial cells

Project description:Abstract. Objectives: Neutrophil extracellular traps (NETs) are extracellular lattices composed of nucleic material bound to neutrophil granule proteins. NETs may play pathogenic roles in development and severity of autoimmune diseases such as systemic lupus erythematosus (SLE), at least in part, through induction of type I interferon (IFN) responses via externalization of oxidized immunostimulatory DNA. A distinct subset of SLE proinflammatory neutrophils (low density granulocytes; LDGs) displays enhanced ability to form proinflammatory NETs that damage the vasculature. We assessed whether NET-bound RNA can contribute to inflammatory responses in endothelial cells and the pathways that mediate this effect. Methods: Expression of newly-synthesized RNA was quantified if healthy control and lupus NETs. The ability of endothelial cells to take up NET-bound RNA and downstream induction of type I IFN responses was quantified. RNAs present in NETs were sequenced and specific small RNAs were tested for induction of endothelial type I IFN pathways. Results: NETs extruded newly-synthesized RNA that was internalized by endothelial cells and this was enhanced when NET nucleic acids were oxidized, particularly in lupus LDG NETs. Internalization of NET-bound total RNA by endothelial cells was dependent on endosomal TLRs and the actin cytoskeleton and induced type I IFN stimulated genes (ISGs). This ISG induction was dependent on NET-associated miR-let7b, a small RNA expressed at higher levels in LDG NETs, which acted as a TLR7 agonist. Conclusion: These results highlight underappreciated roles for small RNAs externalized in NETs in the induction of proinflammatory responses in vascular cells, with implications to lupus vasculopathy.

2023-07-31 | GSE160143 | GEO

Transcriptomic, epigenetic and functional analyses implicate neutrophil diversity in the pathogenesis of systemic lupus erythematosus [ATAC-seq]

Project description:Two subpopulations of low density granulocytes (LDGs) were defined in terms of different gene expression patterns, transcriptional and epigenetic features as well as functions. This study provides insights into the mechanism of immune dysregulation and the vascular damage characteristic of lupus.

2019-11-22 | GSE139359 | GEO

Transcriptomic, epigenetic and functional analyses implicate neutrophil diversity in the pathogenesis of systemic lupus erythematosus [RNA-seq]

2019-11-22 | GSE139358 | GEO

Maturing Neutrophils of Lower Density Associate with Thrombocytopenia in Puumala Orthohantavirus-Caused Hemorrhagic Fever with Renal Syndrome - Human samples

Project description:Puumala orthohantavirus-caused hemorrhagic fever with renal syndrome (PUUV-HFRS) is characterized by significant neutrophil activation. Neutrophils, the most abundant immune cells in circulation, are equipped to respond rapidly to infections and exhibit a notable heterogeneity. This study aims to identify and characterize different neutrophil subsets in the circulation of PUUV-HFRS patients, focusing on low-density granulocytes (LDGs) and normal density polymorphonuclear cells (PMNs). The study finds that PMNs show activation of antiviral pathways, while circulating LDGs increase following acute PUUV-HFRS. Additionally, PUUV-associated LDGs, primarily immature, likely reflect increased bone marrow neutrophil production. Notably, the frequency of LDGs and a "left shift" in blood are associated with the extent of thrombocytopenia, a hallmark of severe HFRS, suggesting a role for maturing neutrophils in disease pathogenesis. Unlike COVID-19 associated LDGs, PUUV LDGs did not exhibit significant immunosuppressive ability, indicating inherent biological differences in LDG responses based on the causative virus or infection kinetics. RNA sequencing was performed on neutrophils isolated from four cohorts: healthy control PMNs, PUUV-infected PMNs, PUUV-infected CD16- LDGs, and PUUV-infected CD16+ LDGs. The RNA sequencing and subsequent bioinformatics analysis were conducted by the Biomedicum Functional Genomics Unit at the Helsinki Institute of Life Science and Biocenter Finland at the University of Helsinki.

2024-06-27 | GSE270609 | GEO

Epigenome profiling reveals significant DNA demethylation of interferon signature genes in lupus neutrophils

Project description:We identified genome-wide DNA methylation patterns within neutrophils and low-density granulocytes of Lupus patients and demographically matched controls

2015-01-21 | GSE65097 | GEO

Epigenome profiling reveals significant DNA demethylation of interferon signature genes in lupus neutrophils

Project description:We identified genome-wide DNA methylation patterns within neutrophils and low-density granulocytes of Lupus patients and demographically matched controls Comparison of 15 Lupus patients vs 15 age-, sex-, and ethnicity-matched controls using the Illumina HumanMethylation 450 beadchip array

2015-01-21 | E-GEOD-65097 | biostudies-arrayexpress

Neutrophils from patients with recurring Panton-Valentine Leukocidin-positive Staphylococcus aureus infections are more sensitive to PVL induced NETosis

Project description:Panton-Valentine Leukocidin (PVL) is a Staphylococcus aureus toxin that binds to and kills human neutrophils resulting in the formation of neutrophil extracellular traps. A subset of individuals colonized with PVL expressing S. aureus suffer from recurring infections. We found that neutrophils from affected individuals display increased spontaneous NET formation after isolation, and increased sensitivity to killing by PVL. Compared to healthy controls, the expression of the target receptors for PVL, CD45 and C5L2, but not CD88, was increased in these patients, and the expression correlated to the amount of PVL-induced NETs produced. NADPH-oxidase activity was not important for PVL induced NETosis as neutrophils from CGD patients produced NETs in response to PVL. Through NET proteome analysis we identified that the protein content of PVL induced NETs is different from mitogen induced NETs. The abundance of the antimicrobial proteins LL37, myeloperoxidase, azurocidin, and proteinase 3 was lower on PVL NETs and PVL-induced NETs were deficient in killing Staphylococcus aureus. Neutrophils from patients that suffer from recurring PVL-positive infections may be more sensitive to PVL-induced NETosis, impairing their ability to combat the infection.

2023-11-23 | PXD025702 | Pride

Transcriptomic Profiling of Neutrophils and Low-Density Granulocytes in COVID-19 Patients

Project description:The severity of COVID-19 is linked to excessive inflammation. Neutrophils represent a critical arm of the innate immune response and are major mediators of inflammation, but their role in COVID-19 pathophysiology remains poorly understood. We conducted transcriptomic profiling of neutrophils obtained from patients with mild and severe COVID-19, as well as from non-infected healthy controls. Additionally, low-density granulocytes (LDGs) from patients with severe COVID-19 were included to understand their unique role. Transcriptomic analysis of polymorphonuclear cells (PMNs), consisting mainly of mature neutrophils, revealed a striking type I interferon (IFN-I) gene signature in severe COVID-19 patients, contrasting with mild COVID-19 and healthy controls. LDGs from severe COVID-19 patients exhibited an immature neutrophil phenotype and lacked this IFN-I signature. These findings underscore the crucial role of neutrophil inflammasomes in driving inflammation during severe COVID-19. The study provides insights into the pathological mechanisms of severe COVID-19 and highlights potential targets for therapeutic intervention.

2024-07-23 | GSE272381 | GEO

Human Neutrophils Phosphoproteome in Systemic Lupus Erythematosus

Project description:This study used proteomic, biomechanical, and functional analyses to further define neutrophil heterogeneity in the context of SLE. Mass spectrometry proteomic and phosphoproteomic analyses were performed in healthy control normal density neutrophils (NDNs), SLE NDNs and in autologous SLE LDGs. Proteomic and phosphoproteomic differences were detected when comparing control to SLE neutrophils and when comparing SLE NDNs to SLE LDGs.

2021-11-04 | PXD021096 | Pride

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