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SINGLE-CELL CHARACTERIZATION OF A MODEL OF POLY I:C-STIMULATED PERIPHERAL BLOOD MONONUCLEAR CELLS IN SEVERE ASTHMA

ABSTRACT: SINGLE-CELL CHARACTERIZATION OF A MODEL OF POLY I:C-STIMULATED PERIPHERAL BLOOD MONONUCLEAR CELLS IN SEVERE ASTHMA

PROVIDER: PRJNA723562 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14294834_1.fastq.gz	Fastqsanger.gz
	SRR14294834_2.fastq.gz	Fastqsanger.gz
	SRR14294835_1.fastq.gz	Fastqsanger.gz
	SRR14294835_2.fastq.gz	Fastqsanger.gz
	SRR14294836_1.fastq.gz	Fastqsanger.gz

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SINGLE-CELL CHARACTERIZATION OF A MODEL OF POLY I:C-STIMULATED PERIPHERAL BLOOD MONONUCLEAR CELLS IN SEVERE ASTHMA

Project description:Background: Asthma has been associated with impaired interferon response. Multiple cell types have been implicated in such response impairment and may be responsible for asthma immunopathology. However, existing models to study the immune response in asthma are limited by bulk profiling of cells. Our objective was to Characterize a model of peripheral blood mononuclear cells (PBMCs) of patients with severe asthma (SA) and its response to the TLR3 agonist Poly I:C using two single-cell methods. Methods: Two complementary single-cell methods, DropSeq for single-cell RNA sequencing (scRNA-Seq) and mass cytometry (CyTOF), were used to profile PBMCs of SA patients and healthy controls (HC). Poly I:C-stimulated and unstimulated cells were analyzed in this study. Results: PBMCs (n=9,414) from five SA (n=6,099) and three HC (n=3,315) were profiled using scRNA-Seq. Six main cell subsets, namely CD4+ T cells, CD8+ T cells, natural killer (NK) cells, B cells, dendritic cells (DCs), and monocytes, were identified. CD4+ T cells were the main cell type in SA and demonstrated a pro-inflammatory profile characterized by increased JAK1 expression. Following Poly I:C stimulation, PBMCs from SA had a robust induction of interferon pathways compared with HC. CyTOF profiling of Poly I:C stimulated and unstimulated PBMCs (n=160,000) from the same individuals (SA=5; HC=3) demonstrated higher CD8+ and CD8+ effector T cells in SA at baseline, followed by a decrease of CD8+ effector T cells after poly I:C stimulation. Conclusions: Single-cell profiling of an in vitro model using PBMCs in patients with SA identified activation of pro-inflammatory pathways at baseline and strong response to Poly I:C, as well as quantitative changes in CD8+ effector cells. Thus, transcriptomic and cell quantitative changes are associated with immune cell heterogeneity in this model to evaluate interferon responses in severe asthma.

2021-04-22 | GSE172495 | GEO

Expression data from airway epithelial cells stimulated with Poly(I:C) from patients with asthma, rhinitis, and healthy controls

Project description:Rhinovirus infections are the most common cause of asthma exacerbations. The complex responses by the airway epithelium to rhinovirus can be captured by gene expression profiling. We hypothesized that the upper and lower airway epithelium exhibit differential responses to double-stranded RNA (dsRNA), and that this is modulated by the presence of asthma and allergic rhinitis. Identification of dsRNA-induced gene expression profiles by microarray of primary nasal and bronchial epithelial cells from the same individuals and examining the impact of allergic rhinitis with and without concomitant allergic asthma on expression profiles. 17 subjects were included in a cross-sectional study (6 allergic asthma and allergic rhinitis; 5 allergic rhinitis; 6 healthy controls). RNA was extracted from isolated and cultured epithelial cells that were stimulated with Poly(I:C) for 24 hours from bronchial brushes and nasal biopsies, and analyzed by microarray (Affymetrix U133+ PM Genechip Array).

2013-10-18 | E-GEOD-51392 | biostudies-arrayexpress

Severe Asthma Microbiome

Project description:Airway microbiota in severe asthma and relationship to asthma clusters and severity

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Severe Asthma Research Program (SARP)

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Nasal DNA methylation differentiates severe from non-severe asthma in African-American (AA) children

Project description:Background: Asthma is highly heterogeneous and severity evaluation is key to asthma management. DNA methylation (DNAm) contributes to asthma pathogenesis. This study aimed to identify nasal epithelial DNAm differences between severe and non-severe asthmatic children and evaluate the impact of environmental exposures. Methods: Thirty-three non-severe and 22 severe asthmatic African-American children were included in an epigenome-wide association study. Genome-wide nasal epithelial DNAm and gene expression were measured. CpG sites associated with asthma severity and environmental exposures and predictive of severe asthma were identified. DNAm was correlated with gene expression. Enrichment for transcription factor (TF) binding sites or histone modifications surrounding DNAm differences were determined. Results: We identified 816 differentially methylated CpG positions (DMPs) and 10 differentially methylated regions (DMRs) associated with asthma severity. Three DMPs exhibited discriminatory ability for severe asthma. Intriguingly, six DMPs were simultaneously associated with asthma, allergic asthma, total IgE, environmental IgE, and FeNO in an independent cohort of children. 27 DMPs were associated with traffic-related air pollution or secondhand smoke. DNAm at 22 DMPs were altered by diesel particles or allergen in human bronchial epithelial cells. DNAm levels at 39 DMPs were correlated with mRNA expression. Proximal to 816 DMPs, three histone marks and several TFs involved in asthma pathogenesis were enriched. Conclusions: Significant differences in nasal epithelial DNAm were observed between non-severe and severe asthma in African-American children, a subset of which may be useful to predict disease severity. These CpG sites are subject to the influences of environmental exposures and may regulate gene expression.

2022-04-15 | GSE161485 | GEO

Rhinovirus-induced gene expression patterns that distinguish between neutrophilic asthma and other asthma inflammatory phenotypes in human peripheral blood mononuclear cells

Project description:Objective: The aim of the current study was to use circulating immune cells to define gene expression patterns that best distinguish between different asthma phenotypes. We hypothesised that analysing gene expression patterns in unstimulated cells would be of limited value, and that variations in gene expression patterns would be most apparent in the setting of RV stimulation. Methods: Peripheral blood mononuclear cells samples from adults with persistent asthma of different inflammatory subtypes were stimulated with RV in vitro with RNA sequencing and bioinformatics used to define gene expression patterns. Results: RV-induced changes in gene expression differed markedly between neutrophilic asthma (NA) and other asthma phenotypes. Expression of many anti-viral immune pathways and their regulators genes was down regulated in NA compared to the other phenotypes, accompanied by enhanced expression of chemokine genes, proinflammatory cytokines and Y chromosome linked genes. These changes were detected in circulating, bone marrow-derived immune cells and were most apparent in RV-stimulated rather than resting cells.

2025-05-04 | GSE202216 | GEO

Serum proteomics of patients with severe asthma

Project description:Serum proteomics was performed using serum collected from patients with severe asthma before and after benralizumab treatment

2026-07-19 | PXD066328 | JPOST Repository

Altered epithelial gene expression in peripheral airways of severe asthma

Project description:Management of severe asthma remains a challenge despite treatment with glucocorticosteroid therapy. The majority of studies investigating disease mechanisms in treatment-resistant severe asthma have previously focused on the large central airways, with very few utilizing transcriptomic approaches. The small peripheral airways, which comprise the majority of the airway surface area, remain an unexplored area in severe asthma and were targeted for global epithelial gene expression profiling in this study.

2017-01-04 | GSE64913 | GEO

Gene expression profiles of healthy mononuclear cells and eosinophils and asthma (moderate and severe) eosinophils

Project description:Gene expression profiles of healthy mononuclear cells and eosinophils and asthma (moderate and severe) eosinophils

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Transcriptomic analysis of induced sputum samples in severe asthma

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