Eosinophil-mediated suppression and Anti-IL-5 enhancement of plasmacytoid dendritic cell interferon responses in asthma
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA719362 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR14134800.fastq.gz | Fastqsanger.gz | |||
| SRR14134801.fastq.gz | Fastqsanger.gz | |||
| SRR14134802.fastq.gz | Fastqsanger.gz | |||
| SRR14134803.fastq.gz | Fastqsanger.gz | |||
| SRR14134804.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 42 |
Similar Datasets
Project description:Blood plasmacytoid dendritic cells (pDCs) purified from anonymous donors were stimulated ex vivo with rhinovirus-16 (RV) in the presence or absence of eosinophil supernatants. Purified pDCs from 8 individuals with moderate-severe asthma, treated or not treated with anti-IL-5/5Rα therapy, were cultured with or without RV. Transcriptome analysis revealed global repression of pDC IFN response patterns by eosinophils, most notably in basal expression of interferon stimulated genes (ISGs). Increased RV-induced IFNα secretion and transcription as well as increased basal ISG expression was detected in pDCs from participants treated with anti-IL-5/5Rα therapy. Our findings highlight a novel mechanism through which T2 inflammation regulates pDC IFNα responses relevant to RV respiratory infections in the context of eosinophilic airway disease and suggest one potential mechanism through with eosinophil-depleting therapies may reduce the severity of RV illness.
2022-01-01 | GSE171378 | GEO
Project description:Therapies targeting interleukin-5 (IL-5) or its receptor (IL-5Rα) are used to treat patients with severe eosinophilic asthma. The therapeutic effect are considered being the suppression of eosinophil activation and elimination. However, the impact of these therapies on mast cells (MCs) and their progenitors has remained largely unexplored. We investigate whether targeting the IL-5 pathway in severe asthma patients could reduce blood MC progenitors
2024-12-05 | GSE263241 | GEO
Project description:Eosinophils are important in fighting parasitic infections and are implicated in the pathogenesis of asthma and allergy. Interleukin-5 (IL-5) is a critical regulator of eosinophil development, controlling proliferation, differentiation and maturation of the lineage. Mice that constitutively express IL-5 have more than 10 fold more eosinophils in the haematopoietic organs than their wild type counterparts. We have identified that much of this expansion is in a population of Siglec-F high eosinophils, which are rare in wild type mice. In this study we assessed transcription in myeloid progenitors, eosinophil precursors and Siglec-F medium and Siglec-F high eosinophils from IL-5 transgenic mice and in doing so have created a useful resource for eosinophil biologists. We have then utilised these populations to construct an eosinophil trajectory based on gene expression and to identify gene sets that are associated with eosinophil lineage progression. Cell cycle genes were significantly associated with the trajectory, and we experimentally demonstrate an increasing trend towards quiescence along the trajectory. Additionally we found gene expression changes associated with constitutive IL-5 signalling in eosinophil progenitors, many of which were not observed in eosinophils.
2018-03-20 | GSE112010 | GEO
Project description:Activated eosinophils is a major cell type to be mainly involved in allergic diseases. Recent studies also indicated that eosinophils play an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD), especially asthma-COPD overlap and/or eosinophil COPD. The aim of this study is to clarify cellular characters of human eosinophils in patients with asthma-COPD overlap and/or eosinophil COPD.
2024-06-20 | PXD052550 | JPOST Repository
Project description:Eosinophils possess distinct functions, being pro-inflammatory in asthma and worm infection on the one hand, while supporting resolution of inflammation and tissue repair on the other hand. We could demonstrate that the immunological pathways causing asthma in the lungs at the same time elicit resolution of arthritis in the joints in an eosinophil-dependent manner. It can be hypothesized that the pro-inflammatory action of eosinophils in the lungs and their homeostatic functions in the synovium are mediated by tissue-specific functional priming. Therefore, single cell RNA sequencing (scRNA-seq) was used to investigate whether distinct eosinophil subsets arise in the lungs and the joints of mice upon combined asthma/arthritis model.
2020-11-12 | GSE153632 | GEO
Project description:To identify regulators of homeostatic eosinophilopoiesis in mice, we took a global approach to identify genome-wide transcriptome and epigenome changes that occur during homeostasis at critical developmental stages, including eosinophil-lineage commitment (eosinophil progenitor [EoP] compared to granulocyte-monocyte progenitor [GMP]) and lineage maturation (eosinophil compared to EoP). Our analyses revealed markedly greater transcriptome alterations associated with eosinophil maturation (1199 genes) compared to eosinophil-lineage commitment (490 genes), highlighting the greater transcriptional investment necessary for differentiation. Our analyses also delineated a 976 gene eosinophil-lineage transcriptome that included a repertoire of 56 transcription factors, many of which have never previously been associated with eosinophils. Epigenomic studies revealed that genes that were specifically induced with eosinophil-lineage commitment in EoPs were “poised” with active chromatin marks in GMPs, despite not being expressed in GMPs. In contrast, a majority of the genes that were highly and specifically induced with maturation in eosinophils was not associated with poised chromatin, suggesting distinct epigenetic regulation between genes induced with lineage commitment compared to genes induced with cell maturation during eosinophil development.
2015-08-13 | GSE69707 | GEO
Project description:Suppression of plasmacytoid dendritic cell migration by compounds derived from natural medicines
| PRJNA704551 | ENA
Project description:Asthma is typically characterized by an imbalance between the expression of proteases and of inhibitors capable of neutralizing such enzymes. Hence, an attractive option for intervening with asthma could be to interfere with asthma-associated proteases. In this study, we exploited this option by assessing the impact of nafamostat, a serine protease inhibitor with known capacity to neutralize mast cell tryptase, on the manifestations of airway responses in a house dust mite (HDM)-based model of experimental asthma. Our findings reveal that nafamostat efficiently suppressed the airway hyperreactivity in HDM-sensitized mice, which was accompanied by a profound reduction in the infiltration of eosinophils and lymphocytes to the airways, and also by suppression of the levels of proinflammatory compounds within the airway lumen.Further, nafamostat caused a marked reduction of eosinophil inflammation in the lung tissue, and we also show that nafamostat had a dampening impact on goblet cell hyperplasia and smooth muscle layer thickening in the lungs of HDM-sensitized animals. To obtain deeper insight into the mechanism by which nafamostat affects parameters of allergic airway inflammation, a transcriptomic analysis was conducted. This analysis revealed, as expected, that the HDM sensitization caused an upregulated expression of numerous proinflammatory genes. Further, the transcriptomic analysis showed that nafamostat suppressed the levels of multiple proinflammatory genes, with a particular impact on genes related to asthma. Altogether, this study provides extensive insight into the ameliorating effect of nafamostat on experimental asthma, and our findings can thereby provide a basis for the further evaluation of nafamostat as a potential therapeutic agent in human asthma.
2023-05-10 | GSE223629 | GEO
Project description:MicroRNA have been implicated in the differentiation and control of eosinophilia in allergic inflammation, however, a detailed investigation of miRNA expression patterns employed during differentiation has not yet been performed [35-37]. The aim of our study is to explore miRNA expression profiling and analysis in silico in order to improve our understanding of the factors and circuits that are involved in the regulation eosinophil growth and differentiation.
2014-08-01 | E-MTAB-2442 | biostudies-arrayexpress
Project description:Humans vary markedly in their propensity to develop asthma, despite often being exposed to similar environmental stimuli. Similarly, mouse strains vary in susceptibility to airways pathology in experimental asthma. Sensitization and aerosol challenge with ovalbumin (OVA) induces eosinophil accumulation, mucus production and airways obstruction in BALB/c and C57BL/6 mice. In contrast, CBA/Ca mice show relatively little pathology. Allergen-induced production of IL-4, IL-5, IL-10 and IFN-g was detected in all three strains, with BALB/c mice generating the highest levels of IL-4, IL-5 and IL-10. Microarray analysis was used to identify genes differentially regulated in lung tissue after OVA challenge. Differentially regulated genes in the lungs of the asthma-susceptible C57BL/6 and BALB/c strains numbered 242 and 145, respectively, whereas only 42 genes were differentially expressed in the resistant CBA/Ca strain. In C57BL/6 mice, transcripts were enriched for adhesion molecules and this was associated with high levels of eosinophil recruitment. Differentially regulated genes in the lungs of only the asthma-susceptible strains numbered 64 and several of these have not previously been associated with asthma. Many of the genes differentially regulated in the susceptible strains were enzymes involved in inflammation. Using network analysis, mRNA for the anti-apoptotic protein survivin was found to be up-regulated in the lungs following allergen challenge. Survivin mRNA and protein were also expressed at high levels in eosinophils recovered by bronchoalveolar lavage from BALB/c and C57BL/6 mice. We propose that rapid apoptosis of lung eosinophils due to low expression of survivin contributes to the limitation of pathology in CBA/Ca mice Humans vary markedly in their propensity to develop asthma, despite often being exposed to similar environmental stimuli. Similarly, mouse strains vary in susceptibility to airways pathology in experimental asthma. Sensitization and aerosol challenge with ovalbumin (OVA) induces eosinophil accumulation, mucus production and airways obstruction in BALB/c and C57BL/6 mice. In contrast, CBA/Ca mice show relatively little pathology. Allergen-induced production of IL-4, IL-5, IL-10 and IFN-g was detected in all three strains, with BALB/c mice generating the highest levels of IL-4, IL-5 and IL-10. Microarray analysis was used to identify genes differentially regulated in lung tissue after OVA challenge. Differentially regulated genes in the lungs of the asthma-susceptible C57BL/6 and BALB/c strains numbered 242 and 145, respectively, whereas only 42 genes were differentially expressed in the resistant CBA/Ca strain. In C57BL/6 mice, transcripts were enriched for adhesion molecules and this was associated with high levels of eosinophil recruitment. Differentially regulated genes in the lungs of only the asthma-susceptible strains numbered 64 and several of these have not previously been associated with asthma. Many of the genes differentially regulated in the susceptible strains were enzymes involved in inflammation. Using network analysis, mRNA for the anti-apoptotic protein survivin was found to be up-regulated in the lungs following allergen challenge. Survivin mRNA and protein were also expressed at high levels in eosinophils recovered by bronchoalveolar lavage from BALB/c and C57BL/6 mice. We propose that rapid apoptosis of lung eosinophils due to low expression of survivin contributes to the limitation of pathology in CBA/Ca mice Changes in gene expression in the lungs of 4 individual of BALB/c mice challenged with OVA were monitored using the lungs of 4 individual BALB/c mice challenged with PBS as the control. The microarray analysis was performed in quadruplicate. Changes in gene expression in the lungs of 4 individual of CBA/Ca mice challenged with OVA were monitored using the lungs of 4 individual CBA/Ca mice challenged with PBS as the control. The microarray analysis was performed in quadruplicate. Changes in gene expression in the lungs of 4 individual of BALB/c mice challenged with OVA were monitored using the lungs of 4 individual CBA/Ca mice challenged with OVA as the control. The microarray analysis was performed in quadruplicate. Twelve dual channel microarray slides were used in the overall design of this experiment.
2010-05-18 | E-GEOD-15345 | biostudies-arrayexpress