Epigenetic differences in long non-coding RNA expression in Finnish and Russian Karelia teenagers with contrasting risk of allergy and asthma
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE200158 | GEO | 2024/04/04
REPOSITORIES: GEO
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Project description:CD4+ helper T cells (TH) and regulatory T cells (Treg) that respond to common allergens play an important role in driving and dampening airway inflammation in patients with asthma. Until recently, direct, unbiased molecular analysis of allergen-reactive TH and Treg cells has not been possible. To better understand the diversity of these T cell subsets in allergy and asthma, we analyzed the single-cell transcriptome of ~50,000 house dust mite (HDM) allergen-reactive TH cells and Treg cells from asthmatics with HDM allergy and from three control groups: asthmatics without HDM allergy and non-asthmatics with and without HDM allergy. Our analyses show that HDM allergen-reactive TH and Treg cells are highly heterogeneous, and certain subsets are quantitatively and qualitatively different in subjects with HDM-reactive asthma. The number of interleukin (IL)-9 expressing HDM-reactive TH cells is greater in asthmatics compared with non-asthmatics with HDM allergy, and display enhanced pathogenic properties. More HDM-reactive Th and Treg cells expressing the interferon-response signature (THIFNR and TregIFNR) are present in asthmatics without HDM allergy compared with those with HDM allergy. In cells from these subsets (THIFNR and TregIFNR), expression of TNFSF10 was enriched; its product, TRAIL, dampens activation of TH cells. These findings suggest that the THIFNR and TregIFNR subsets may dampen allergic responses, which may help explain why only some people develop TH2 responses to nearly ubiquitous allergens.
2020-06-10 | GSE146170 | GEO
Project description:CD4+ helper T cells (TH) and regulatory T cells (Treg) that respond to common allergens play an important role in driving and dampening airway inflammation in patients with asthma. Until recently, direct, unbiased molecular analysis of allergen-reactive TH and Treg cells has not been possible. To better understand the diversity of these T cell subsets in allergy and asthma, we analyzed the single-cell transcriptome of ~50,000 house dust mite (HDM) allergen-reactive TH cells and Treg cells from asthmatics with HDM allergy and from three control groups: asthmatics without HDM allergy and non-asthmatics with and without HDM allergy. Our analyses show that HDM allergen-reactive TH and Treg cells are highly heterogeneous, and certain subsets are quantitatively and qualitatively different in subjects with HDM-reactive asthma. The number of interleukin (IL)-9 expressing HDM-reactive TH cells is greater in asthmatics compared with non-asthmatics with HDM allergy, and display enhanced pathogenic properties. More HDM-reactive Th and Treg cells expressing the interferon-response signature (THIFNR and TregIFNR) are present in asthmatics without HDM allergy compared with those with HDM allergy. In cells from these subsets (THIFNR and TregIFNR), expression of TNFSF10 was enriched; its product, TRAIL, dampens activation of TH cells. These findings suggest that the THIFNR and TregIFNR subsets may dampen allergic responses, which may help explain why only some people develop TH2 responses to nearly ubiquitous allergens.
2020-06-10 | GSE146046 | GEO
Project description:Background Previously, we investigated skin microbiota and blood cell gene expression in Finnish and Russian teenagers with contrasting incidence of allergic conditions. The microbiota and transcriptomic signatures were distinctly different, with high Acinetobacter abundance and suppression of genes regulating innate immune response in healthy subjects. Objective Here, we investigated long non-coding RNA (lncRNA) expression profiles of blood mononuclear cells (PBMC) from healthy and allergic subjects, to identify lncRNAs that act at the interphase of microbiome-mediated immune homeostasis in allergy/asthma. Methods Genome-wide co-expression network analyses of blood cell lncRNA/mRNA expression was integrated with skin microbiota profiles of Finnish (69) and Russian (75) subjects. Selected lncRNAs were validated by stimulation of cohort-derived PBMCs and a macrophage cell model with birch pollen allergen (Betv1) or lipopolysaccharide, respectively. Results Finnish and Russian PBMCs were differentiated by 3,818 lncRNA transcripts. In the Finnish subjects with high prevalence of allergy and asthma, a subset of 37 downregulated lncRNAs (including, FAM155A-IT1 and LOC400958) were identified. They were part of a co-expression network with 20 genes known to be related to asthma and allergic rhinitis (R > 0.95). Incidentally, all these 20 genes were also components of pathways corresponding to cellular response to bacterium. The Finnish and Russian samples were also differentiated by the abundance of 176 bacterial OTU (operational taxonomic units). The subset of 37 lncRNAs, associated with allergy, was most correlated with the abundance of Acinetobacter (R > +0.5), Jeotgalicoccus (R > +0.5), Corynebacterium (R < −0.5) and Micrococcus (R < −0.5). Conclusion In Finnish and Russian teenagers with contrasting allergy and asthma prevalence, epigenetic differences in lncRNA expression appear to be important components of the underlying microbiota-immune interactions. Unraveling the functions of the 37 differing lncRNAs may be the key to understanding microbiome-immune crosstalk, and to develop clinically relevant biomarkers.
| S-EPMC9234912 | biostudies-literature
Project description:MAP Project 25 asthma blood samples run for the UCSD Microbiome Core
2022-09-01 | MSV000090246 | MassIVE
Project description:Features of the bronchial bacterial microbiome associated with atopy, asthma and responsiveness to inhaled corticosteroid treatment.
| PRJEB15533 | ENA
Project description:Single-cell transcriptomic analysis of allergen-specific T cells in allergy and asthma
| PRJNA609639 | ENA
Project description:In this study we present the first genome-wide expression profiling of peripheral B cells by massive parallel RNA sequencing in patients with allergic asthma validating the discovery potential of this approach in allergy.
2014-08-28 | GSE52742 | GEO
Project description:Background: Clinical transcriptomics of peripheral blood mononuclear cells (PBMC) are coming into focus as a surrogate approach for prognosis, diagnosis, biomarker discovery and examination disease mechanisms. However, bioassays paired with transcriptomic analytic tools are yet to be developed and made available at point of care. Harnessing personal dynamic genomic responses to tailor patient asthma treatment or prevent disease exacerbations remain unmet medical needs. Method: We developed a rhinovirus-stimulated peripheral blood based-assay (virogram assay) coupled with single-subject analytics (N-of-1-patwhays) to capture dynamic genome-wide expression and dysregulated pathways to retrospectively predict childhood asthma exacerbation. We hypothesized that some genomic factors might predispose any given individual, healthy or asthmatic, to a set of similar transcriptional responses to rhinovirus stimulation. We first generated a classifier from paired sample microarrays, control and stimulated PBMC from healthy subjects and applied this classifier on the transcriptomic analysis of control and HRV-stimulated PBMC samples (virogram assay) from children with asthma. Results: The analysis of the different genomic responses of single-subject paired PBMC samples (HRV-stimulated and control) derived from healthy individuals (external dataset) enabled the discovery of dysregulated pathways related to acquired immunity, epigenetics and morphogenesis. The classifier built on these results and applied on the transcriptional analysis derived from the virogram assay predicted that the risk of asthma exacerbation among asthmatic subjects with an accuracy of 70%. Conclusion: We provide evidence that clinical prognosis can be predicted with a PBMC based-bioassay aligned with adequate single-subject analytics to assess dynamic transcriptomic response to specific disease-associated stimuli.
2016-05-01 | GSE68479 | GEO
Project description:In this study we present the first genome-wide expression profiling of peripheral B cells by massive parallel RNA sequencing in patients with allergic asthma validating the discovery potential of this approach in allergy. RNA-seq was used to asses expression differences in B CD19 Lymphocytes from house dust mite allergic patients and healthy controls.
2014-08-28 | E-GEOD-52742 | biostudies-arrayexpress
Project description:In this proof-of-concept study, we piloted a precision endotyping approach focused on DNA methylation biomarkers (CpG methylation) which are regulatory base modifications to DNA that influence cellular immune responses across the life course. The aims of this study were to (a) pilot a precision endotyping approach in a selected group of children from the Rochester prospective cohort who exhibited characteristics of high respiratory infection allergy/asthma prone (IAP) and low vaccine responsiveness (LVR) in early childhood, compared to non-respiratory infection allergy/asthma prone (NIAP) children and (b) assess whether stimulation of PBMCs with stimuli a vaccine adjuvant that activating activates a pattern recognition receptors (PRRs) could re-shape the epigenome.
2024-08-05 | GSE272991 | GEO