Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Airway epithelial cells prime plasmacytoid dendritic cells to respond to pathogens via secretion of growth factors

ABSTRACT: Plasmacytoid dendritic cells (PDCs) are thought to play a role in mucosal tolerance as well as in defense against respiratory viruses because of their propensity to secrete high levels of type I interferons (IFN). The functions of PDCs in the lung can be influenced by airway epithelial cells (AECs) because of their close proximity. We examined the effect of human primary AECs on PDC functions by performing RNA-sequencing of PDCs after co-culture with air liquid interphase differentiated AECs. Co-culture led to the upregulation of transcripts included those encoding cytosolic sensors of DNA, ZBP-1,IRF-3 and NFkB as well as genes involved in amplification of the type 1 IFN response, such as IFNAR1, JAK/STAT, ISG15. These data highlight possible mechanisms to enhance the production of type-I IFN in the airways, which is critical for host defense against respiratory infections

ORGANISM(S): Homo sapiens

PROVIDER: GSE119542 | GEO | 2021/09/04

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

IFN? expression is restricted to a subpopulation of splenic pDCs exhibiting a specific immune modulatory transcriptome signature

Project description:Type I IFNs are critical in initiating protective antiviral immune responses and plasmacytoid DCs (pDCs) represent a major source of these cytokines. Here we show that only few pDCs are capable to produce IFN? after virus infection or CpG stimulation. Utilizing IFN?/YFP reporter mice, we identify these IFN?-producing cells in the spleen as a CCR9+CD9- pDC subset exclusively localized within the T/B cell zones. IFN?-producing pDCs exhibit a distinct transcriptome profile with higher expression of genes encoding cytokines and chemokines, facilitating T cell recruitment and activation. These distinctive characteristics of IFN?-producing pDCs are independent of the type I IFN receptor mediated feedback loop. Furthermore, IFN?-producing pDCs exhibit enhanced CCR7-dependent migratory properties in vitro and in a peritoneal inflammation model they effectively recruit T cells in vivo. We define “professional type I IFN-producing cells” as a distinct subset of pDCs specialized in coordinating cellular immune responses. IFN? associated gene expression in ex vivo sorted IFN?/YFPpos vs. IFN?/YFPneg splenic pDCs was measured at 6 hr after i.v. injection of CpG 1668 complexed to DOTAP. Two independent experiments were performed using pooled samples of at least 12 mice per experiment.

2015-05-27 | E-GEOD-68788 | biostudies-arrayexpress

Purified CD123+BDCA4+ plasmacytoid dendritic sorted cell-population derived from IFN signature positive primary Sjögren’s syndrome patients and IFN signature negative primary Sjögren’s syndrome patients compared to Healthy Control individuals

Project description:The IFN type I signature is present in over half of primary Sjögren’s syndrome (pSS) patients and associated with higher disease-activity and autoantibody presence. Plasmacytoid dendritic cells (pDCs) are considered to be the source of enhanced IFN type I expression. The objective of this study was to unravel the molecular pathways underlying IFN type I bioactivity in pDCs of pSS patients. We used microarray gene expression analysis to detail the programme of gene expression underlying IFN type I bioactivity in pDCs of primary Sjogrens' Syndrome patients.

2016-09-28 | GSE83558 | GEO

Proteomic and single-cell transcriptomic dissection of human plasmacytoid dendritic cell response to influenza virus

Project description:Plasmacytoid dendritic cells [pDCs] represent a rare innate immune subset uniquely endowed with the capacity to produce substantial amounts of type-I interferons [IFN-I]. This function of pDCs is critical for effective antiviral defenses and has been implicated in autoimmunity. While IFN-I and select cytokines have been recognized as pDC secreted products, a comprehensive agnostic profiling of the pDC secretome in response to a physiologic stimulus has not been reported. We applied LC-MS/MS to catalogue the repertoire of proteins secreted by pDCs in response to challenge with live influenza H1N1. Additionally, using single-cell RNA-seq [scRNA-seq], we perform multidimensional analyses of pDC transcriptional diversification following stimulation. Our data reveal an abundance of protein species released by pDCs in addition to IFN-I, and evidence highly specialized roles within the pDC population ranging from dedicated cytokine super-producers to cells with APC-like functions. Moreover, dynamic expression of transcription factors and surface markers characterize activated pDC fates.

2021-11-12 | MSV000088375 | MassIVE

Single-cell analysis reveals stochastic regulation of type I IFN production by plasmacytoid dendritic cells and identifies host-derived environmental cues as amplifier of type I IFN production

Project description:Type I interferon (IFN) is a key driver of immunity to infections and cancer. Plasmacytoid dendritic cells (pDCs) are uniquely equipped to produce large quantities of type I IFN but the mech-anisms that control this process are poorly understood. Here, we developed a droplet-based microfluidic platform and investigated type I IFN production in human pDCs at the single-cell level. We show that type I IFN but not TNF alpha production is limited to a small subpopulation of individually stimulated pDCs and controlled by stochastic gene regulation. Combining single-cell cytokine analysis with single-cell RNA-seq profiling reveals no evidence for a pre-existing subset of type I IFN-producing pDCs. Intriguingly, by modulating the droplet microenvironment, we demonstrate that vigorous pDC population responses are driven by a type I IFN amplification loop. Our study highlights the significance of stochastic gene regulation and suggests strategies to dissect the characteristics of immune responses at the single-cell level.

2018-08-22 | GSE114161 | GEO

CITE-seq analysis of Mycobacterium tuberculosis infected B6 and Sp140-deficient mouse lungs

Project description:Mycobacterium tuberculosis (Mtb) causes 1.5 million deaths annually. Active tuberculosis correlates with a neutrophil-driven type I interferon (IFN) signature, but the underlying cellular mechanisms remain poorly understood. We found that interstitial macrophages (IMs) and plasmacytoid dendritic cells (pDCs) are dominant producers of type I IFN during Mtb infection in mice and non-human primates, and pDCs localize near human Mtb granulomas. Depletion of pDCs reduces Mtb burdens, implicating pDCs in tuberculosis pathogenesis. During IFN-driven disease, we observe abundant DNA-containing neutrophil extracellular traps (NETs) known to activate pDCs. Single cell RNA-seq indicates that type I IFNs act on IMs to impair their responses to IFNg, a cytokine critical for Mtb control. Cell type-specific disruption of the type I IFN receptor suggests IFNs act on IMs to inhibit Mtb control. We propose pDC-derived type I IFNs, driven by NETs, act on IMs to drive bacterial replication, further neutrophil recruitment, and active tuberculosis disease.

2024-01-12 | GSE216023 | GEO

Bulk RNA-seq analysis of Mycobacterium tuberculosis infected Sp140-sufficient and -deficient mouse lungs with and without pDC depletion

2024-01-12 | GSE232922 | GEO

Bulk RNA-seq analysis of bone marrow-derived macrophages stimulated with various cytokines

2024-01-12 | GSE232827 | GEO

NCF1-dependent low production of reactive oxygen species in plasmacytoid dendritic cells exacerbates lupus

Project description:Low capacity to produce reactive oxygen species (ROS) due to mutations in neutrophil cytosolic factor 1 (NCF1/p47phox) is strongly associated with lupus development both in humans and mouse models. Here, we aim to identify the major mechanisms of the Ncf1-disease association. We found that plasmacytoid dendritic cells (pDCs), the most potent producers of type I IFNs, exacerbate pristane-induced lupus in ROS-defective Ncf1-mutant and human NCF1-339 variant carrying mice. ROS deficiency in mouse models with Ncf1 mutation or human NCF1-339 variant leads to enhanced pDC generation via the TLR7/AKT/mTOR pathway and accumulation at sites of inflammation, resulting in an increased IFNα secretion. The produced IFNα further stimulates the JAK1/STAT1 pathway, which we found is hyperreactive in ROS-deficient pDCs. This, in turn, leads to increased type I IFN signature and enhanced proinflammatory responses. Our discoveries explain the causative effect of dysfunctional Ncf1 and pathogenicity of pDCs in lupus.

2023-03-12 | PXD035964 | Pride

TLR-mediated type I IFN induction in pDCs requires the rapamycin-sensitive PI3K-mTOR-p70S6K pathway

Project description:Robust type I interferon (IFN-alpha/beta) production in plasmacytoid dendritic cells (pDCs) is critical for anti-viral immunity. Here we demonstrated a role for the mammalian target of rapamycin (mTOR) pathway in regulating interferon production by pDCs. Inhibition of mTOR or the ‘downstream’ mediators of mTOR p70S6K1,2 kinases during pDC activation via Toll-like receptor 9 (TLR9) blocked the interaction of TLR9 with the adaptor MyD88 and the subsequent activation of interferon response factor 7 (IRF7), resulting in impaired IFN-alpha production. Microarray analysis confirmed that inhibition of mTOR by the immunosuppressive drug rapamycin suppressed anti-viral and anti-inflammatory gene expression. Consistent with this, targeting rapamycin-encapsulated microparticles to antigen-presenting cells in vivo resulted in a diminution of IFN-alpha production in response to CpG DNA or the yellow fever vaccine virus strain 17D. Thus, mTOR signaling plays a critical role in TLR-mediated IFN-alpha responses by pDCs. CpGA is a TLR9 agonist. pDCs were isolated from mouse spleen or human PBMC. The effect of rapamycin on pDCs IFN-alpha production as induced by TLR ligands was studied. The mechanism of rapamycin effect was dissected in RAW cell line.

2008-12-01 | E-GEOD-12218 | biostudies-arrayexpress

The regulation and pharmacological modulation of immune complex induced type III IFN production by plasmacytoid dendritic cells [RNA-seq]

Project description:Objective: Patients with Systemic Lupus Erythematosus (SLE) have an ongoing interferon (IFN) production due to an activation of plasmacytoid dendritic cells (pDCs), which can be triggered to type I IFN synthesis by RNA containing immune complexes (RNA-IC). Considering emerging data suggesting a role of type III interferon (IFN) in the SLE disease process, we asked if RNA-IC can induce type III IFN production in pDC, and how this production can be regulated. Methods: Peripheral blood mononuclear cells (PBMCs) or immune cell subsets were isolated from healthy blood donors or SLE patients and stimulated with IC containing U1 snRNP and SLE-IgG (RNA-IC). Hydroxychloroquine (HCQ) and an interleukin receptor 1 associated kinase 4 inhibitor (IRAK4i) were added to cell cultures. Cytokine mRNA levels were determined with a microarray and protein levels with immunoassays. Single-cell RNA-sequencing of pDCs using ddSEQ technology was performed. Results: Type III IFN mRNA and protein was induced in RNA-IC stimulated pDC-NK and pDC-B cell co-cultures. A subset of activated pDCs (3%) expressed both type III and type I IFN mRNA. IFN-λ2, IFN-α2b, interleukin (IL)-3, IL-6 or granulocyte-macrophage colony stimulating factor (GM-CSF) enhanced IFN-λ1/3 production 2-5-fold. HCQ and an IRAK4i blocked the RNA-IC-triggered IFN-λ1/3 production (p<0.01). IFN-α2b and GM-CSF increased the proportion of SLE patients producing IFN-λ1/3 in response to RNA-IC from 11 to 33%. Conclusions: Type III IFN production is triggered by RNA-IC in pDCs in a TLR-MyD88-dependent manner, enhanced by NK and B cells as well as several pro-inflammatory cytokines. These results support a contributing role for both type I and type III IFNs in SLE, which needs to be considered when targeting the IFN system in this disease.

2020-05-23 | GSE148902 | 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