Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Neutrophil extracellular DNA traps promote neutophils migration and activation by TLR9 signalling in type 2 autoimmune pancreatitis

ABSTRACT: Neutrophil infiltration around the pancreatic ducts has been found to be associated with type 2 autoimmune pancreatitis (AIP). However, the functional role and clinical importance of neutrophils migration on the progress of pancreatitis is not fully understood. Here, we found that neutrophil extracellular traps (NETs) are abundant around the pancreatic duct in type 2 AIP patients. Moreover, we observed the expression of TLR9 is higher in pancreatic ductal epithelial Cells (HPDEC) in type 2 AIP patients than in other pancreatic diseases. TLR9 acts as a NET-DNA receptor on HPDEC that senses extracellular DNA and subsequently activates the NF-κB pathway to attract neutrophils motility and induce NETs formation. In addition, the TLR9 antagonist hydroxychloroquine (HCQ) can effectively inhibit the activation of inflammatory pathways, reduce the migration of neutrophils and block the positive feedback mechanism, which can be used as a potential target drug for the clinical treatment of type 2 AIP.

ORGANISM(S): Homo sapiens

PROVIDER: GSE272893 | GEO | 2025/07/23

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Transcription profiling of human pancreas from patients with autoimmune pancreatitis and alcohol-induced chronic pancreatitis

Project description:Autoimmune pancreatitis (AIP) is a recently identified disease of the pancreas with unknown etiology and antigens. The aim of this study was to determine new target antigens and differentially regulated genes and proteins by means of transcriptomics and proteomics and to validate them in patients with autoimmune pancreatitis. Here we report a distinct downregulation at the RNA and protein level of pancreatic proteases (anionic trypsinogen, cationic trypsinogen, mesotrypsinogen, elastase IIIB) and pancreatic stone protein in autoimmune pancreatitis in comparison to alcohol-induced chronic pancreatitis.

2008-12-31 | E-MEXP-804 | biostudies-arrayexpress

RNA-Seq of isolated pancreatic stellate cells from mice with autoimmune pancreatitis and chronic pancreatitis

Project description:Autoimmune pancreatitis (AIP) is a disease with unclear immunologic triggers. This study shows that the pancreatic stellate cells(PSCs) are involved in the regulation of the immune response and can cause autoimmunity when the NF-κB signalling in these cells is disrupted. The PSCs were isolated from animals which show autoimmune pancreatitis (NEMO knockout group) or chronic pancreatitis (NEMO wildtype group).

2023-06-30 | E-MTAB-7337 | biostudies-arrayexpress

Transcriptome profiling of the pancreas samples from animals showing autoimmune pancreatitis and chronic pancreatitis

Project description:Autoimmune pancreatitis (AIP) is a disease with unclear immunologic triggers. This study shows that the pancreatic stellate cells are involved in the regulation of the immune response and can cause autoimmunity when the NF-κB signalling in these cells is disrupted.

2022-03-31 | E-MTAB-7274 | biostudies-arrayexpress

NFE2-driven neutrophil polarization promotes pancreatic cancer liver metastasis progression

Project description:Pancreatic cancer liver metastasis (PCLM) is an important factor leading to dismal prognosis. The adaptive remodeling of the tumor microenvironment (TME), especially the role of neutrophil in liver metastasis remains elusive. Here we combined single-cell sequencing combined with spatial transcriptomics on patients’ samples to characterize the landscape of PCLM, and explored the functional diversity possessed by neutrophils infiltrated in liver metastases. We identified the pivotal Neutrophils_S100A12 cluster capable of promoting metastatic progression by releasing neutrophil extracellular traps (NETs); spatially, Neutrophils_S100A12 cells are specifically distributed at the invasive front of the metastatic lesions. Mechanistically metastatic TME activates canonical TGF-β/SMAD3 signaling within neutrophil, resulting in NFE2-mediated phenotypic polarization; furthermore NFE2 induces NETs generation by up-regulating PADI4 expression. Interference with NFE2 activation in neutrophils prevents phenotypic conversion and reduces liver metastasis. Our data demonstrate that NFE2-mediated neutrophil polarization in PCLM is a potential target for anti-metastatic therapy.

2025-01-18 | GSE281288 | GEO

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

The cytosolic DNA sensor cGAS recognizes Neutrophil Extracellular Traps

Project description:Neutrophil Extracellular Traps (NETs) are structures consisting of chromatin and antimicrobial molecules that are released by neutrophils during a form of regulated cell death called NETosis. NETs trap invading pathogens, promote coagulation and activate myeloid cells to produce Type I interferons (type I IFN), proinflammatory cytokines that regulate the immune system. The mechanism of NET recognition by myeloid cells is not yet clearly identified. Here we show that macrophages and other myeloid cells phagocytose NETs. Once in phagosomes, NETs translocate to the cytosol, where they activate the DNA sensor cyclic GMP-AMP synthase (cGAS) and induce type I IFN expression. cGAS recognizes the DNA backbone of NETs. Interestingly, the NET associated serine protease Neutrophil Elastase (NE) mediates the activation of the pathway. We confirmed that NETs activate cGAS in vivo. Thus, our findings identify cGAS as a major sensor of NETs, mediating the immune activation during infection and in auto-immune diseases.

2021-02-18 | PXD015579 | Pride

Neutrophil extracellular traps in the central nervous system: a novel therapeutic target in pneumococcal meningitis.

Project description:Neutrophils are crucial mediators of host defense and are recruited to the central nervous system in large numbers during acute bacterial meningitis caused by S. pneumoniae. Neutrophils can release neutrophil extracellular traps (NETs) during infections to trap and kill bacteria. Intact NETs are fibrous structures and mainly consist of decondensed DNA and neutrophil-derived antimicrobial proteins. We report the extensive presence of NETs in the cerebrospinal fluid of patients with pneumococcal meningitis, and absence of NETs in other forms of meningitis caused by viruses, Borrelia and subarachnoid hemorrhage. In a rat model of meningitis, a clinical strain of pneumococci induced NET formation in the cerebrospinal fluid. Importantly, disrupting NETs using DNase I significantly reduced bacterial load, demonstrating that NETs contribute to the pathogenesis of pneumococcal meningitis in vivo. Targeting NETs using DNase may represent a novel indication for an already approved drug as a non-antibiotic therapeutic option to treat acute pneumococcal meningitis.

2019-11-12 | PXD011546 | Pride

NETOME: The Molecular Characterization of Neutrophil Extracellular Traps (NETs)

Project description:Neutrophils are necessary in mamalian’s life and are the most abundant type of white blood cells in humans with biological roles relevant to inflammation and the entire host response. The release of neutrophil extracellular DNA in innate immune cells provides specific response to bacteria and fungi. Neutrophil Extracellular Traps (NETs) act as antimicrobial agents and activators of immune response through release of the nuclear content into the extracellular space. Although great strides have been made in dissecting cellular and molecular pathways that control NET formation, the exact molecular composition of released NETs has not been elucidated. Here, we open the field of NETOMIC studies through isolation of NETs in combination with shotgun genomics and proteomics. This study reveals the molecular composition of NETs and specific expression regions of NETs induced in a sterile inflammation system. The existence of an in vitro NET isolation model allowed for an unprecedented amount of replicability. Additional studies are needed to verify the specificity of these sequences in the context of human health and disease upon diverse neutrophil microbial challenges.

2022-10-25 | PXD016143 | Pride

Proteomic analysis of neutrophil extracellular traps (healthy control, rheumatoid arthritis, systemic lupus erythematosus)_C4PR_LIV

Project description:Neutrophil Extracellular Traps (NETs) are chromatin-derived extracellular structures that are expelled from neutrophils in response to infectious or inflammatory stimuli. NET DNA structures are decorated with proteins including histones, myeloperoxidase and neutrophil elastase. NETs are implicated in the development of auto-immunity in diseases including rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) through the externalisation of intracellular neoepitopes e.g. dsDNA and nuclear proteins in SLE and citrullinated peptides in RA. The aim of this work was to use quantitative proteomics to identify and measure NET proteins produced by neutrophils from healthy individuals, and from patients with RA and SLE.

2019-02-18 | PXD011796 | Pride

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

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