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Single-cell transcriptomic analysis of allergen-specific T cells in allergy and asthma [scRNA-Seq]

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE146170 | GEO | 2020/06/10

REPOSITORIES: GEO

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Single-cell transcriptomic analysis of allergen-specific T cells in allergy and asthma [RNA-Seq]

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

Effect of allergen sensitization on gene expression in dendritic cells from neonates of asthmatic vs control mothers

Project description:This study aims to demonstrate the link between epigenome-wide methylation aberrations at birth and genomic transcriptional changes upon allergen sensitization that occur in the neonatal dendritic cells (DC) due to maternal asthma. In an in vivo model reproducing human epidemiology findings, maternal but not paternal asthma predisposes the neonate to increased asthma risk, the effect is allergen-independent and is not genetic or environmental. Earlier we demonstrated that neonates of asthmatic mothers are born with a functional skew in splenic DCs that mediates the early-life asthma origin. These allergen-naive cells convey allergy responses to normal recipients, however minimal to no transcriptional or phenotypic changes were found to explain the functional pro-allergic alterations. In this study we profiled both allergen-naïve dendritic cells, and cells after allergen sensitization in vivo. We found that while allergen-naive DCs from asthma-at-risk neonates have minimal transcriptional change compared to controls, upon allergen sensitization, multiple genes with pre-existing epigenetic alterations show significant transcriptional change. . 24 samples from 2 batches, 3-4 replicates in each of 4 groups

2013-06-01 | E-GEOD-44678 | biostudies-arrayexpress

Transcription profiling of human airway epithelial cell response to LPS and house dust mite antigen

Project description:Allergic asthmatic, allergy only, asthma only (no allergy), and non-allergic non-asthmatic (control) subjects underwent bronchoscopy with instillation of saline, lipopolysaccharide (LPS), and house dust mite antigen in separate subsegmental bronchi. Airway epithelial cells were collected four hours later (three samples per subject). RNA was extracted from these cells for microarray analysis. Experiment Overall Design: There are four main phenotypic groups: Experiment Overall Design: 1. control (no allergy or asthma) Experiment Overall Design: 2. allergy only (no asthma) Experiment Overall Design: 3. asthma only (no allergy) Experiment Overall Design: 4. allergy and asthma Experiment Overall Design: and three exposures: saline, house dust mite antigen (HDM), and LPS. Samples from the different exposures were all collected at the same time: four hours after instillation. The hybridizations were carried out in two main "batches": samples in batch 1 were processed in mid 2004, samples in batch 2 about a year later in 2005. There is a clear "batch effect": differences between expression profiles from the two batches (likely caused by technical differences between hybridization and scanning methods). This should be considered when analyzing the data.

2009-10-11 | E-GEOD-8190 | biostudies-arrayexpress

Transcription profiling of human bronchoalveolar to investigate airway inflammatory cell response to lipopolysaccharide and house dust mite antigen

Project description:Allergic asthmatic, allergy only, asthma only (no allergy), and non-allergic non-asthmatic (control) subjects underwent bronchoscopy with instillation of saline, lipopolysaccharide (LPS), and house dust mite antigen in separate subsegmental bronchi. Bronchoalveolar lavage (BAL) fluid was collected four hours later (three samples per subject). Inflammatory cells from each specimen were isolated and RNA was extracted for microarray analysis. Experiment Overall Design: There are four main phenotypic groups: Experiment Overall Design: 1. control (no allergy or asthma) Experiment Overall Design: 2. allergy only (no asthma) Experiment Overall Design: 3. asthma only (no allergy) Experiment Overall Design: 4. allergy and asthma Experiment Overall Design: and three exposures: saline, house dust mite antigen (HDM), and LPS. Experiment Overall Design: Samples from the different exposures were all collected at the same time: four hours after instillation. The hybridizations were carried out in two main 'batches': samples in batch 1 were processed in mid 2004, samples in batch 2 about a year later in 2005. There is a clear 'batch effect': differences between expression profiles from the two batches (likely caused by technical differences between hybridization and scanning methods). This should be considered when analyzing the data.

2009-10-10 | E-GEOD-5272 | biostudies-arrayexpress

Effect of allergen sensitization on gene expression in dendritic cells from neonates of asthmatic vs control mothers

2013-06-01 | GSE44678 | GEO

Epigenomic analysis of neonatal dendritic cells in mice with increased allergic susceptibility

Project description:RATIONALE: In a mouse model of maternal transmission of asthma risk (J. Immunol 170:1683, 2003), baby mice of asthmatic (As), but not normal (Nrm), mothers show increased susceptibility to allergy. We previously showed that adoptive transfer to normal baby mice of dendritic cells (DCs) harvested from asthma-susceptible but allergen-naÃ¯ve neonates reproduces the increased susceptibility to asthma. Hence, the maternal effect is mediated by altered neonatal DCs, which skew immune responses towards a pro-allergic Th2 phenotype. To identify potential molecular mechanisms, we performed epigenomic profiling of isolated neonatal DCs. METHODS: BALB/c mice were sensitized by 2 i.p. injections of ovalbumin (OVA) in alum and repeatedly challenged with OVA aerosols (As) prior to mating with normal males. Purified splenic CD11c+ DCs of 14-day old allergen-naÃ¯ve offspring from these As and control Nrm mothers were isolated using magnetic beads. Methylation profiles of genomic DNA were obtained using Switchgear epigenomic chip arrays. After normalization and background correction analysis using significance analysis for microarrays (SAM) and ANOVA was performed. RESULTS: We identified 300 to 6000 (depending on stringency) chromosomal regions with significantly different methylation status, (2 â 10 fold). Clustering methods and pathway analysis identified several interrelated gene groups that merit further study. CONCLUSION: Maternal asthma causes multiple significant epigenetic changes in neonatal dendritic cells. Keywords: Dendritic cells, genomic DNA, DNA methylation, allergy, asthma The analysis includes 9 samples of genomic DNA from isolated splenic CD11c+ dendritic cells (>95% pure) per group. The two groups are neonates born to mothers with induced allergy to ovalbumin, and normal control neonates. All neonates are genetically and environmentally identical, and allergen-naive.

2010-06-24 | E-GEOD-13380 | biostudies-arrayexpress

A model of human asthma exacerbation identifies novel transcriptional programs and pathogenic cell circuits in the lower airway mucosa specific to allergic asthma

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2023-02-24 | GSE193816 | GEO

Transcriptional changes in alveolar macrophages from adults with asthma after intrabronchial allergen challenge.

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