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Distinct epithelial gene expression phenotypes in childhood respiratory allergy

ABSTRACT: Distinct epithelial gene expression phenotypes in childhood respiratory allergy

OTHER RELATED OMICS DATASETS IN: E-GEOD-19187E-GEOD-19182

PROVIDER: PRJNA120675 | ENA |

REPOSITORIES: ENA

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Distinct epithelial gene expression phenotypes in childhood respiratory allergy

Project description:This SuperSeries is composed of the following subset Series: GSE19182: Gene expression profiling of differentiated HNECs stimulated by IL4, IL13, IFNalpha, IFNbeta, IFNgamma and controls GSE19187: Nasal epithelium gene expression profiling in child respiratory allergic disease Refer to individual Series

2012-01-05 | E-GEOD-19190 | biostudies-arrayexpress

Distinct epithelial gene expression phenotypes in childhood respiratory allergy

Project description:This SuperSeries is composed of the SubSeries listed below.

2012-01-05 | GSE19190 | GEO

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Project description:The prevalence of respiratory allergy in children is increasing. Epigenetic changes (e.g. DNA methylation) are plausible underlying molecular mechanisms. Longitudinal birth cohorts are instrumental to study the relation between early-life environmental factors and the development of complex diseases. Our AXA Research Fund and Cefic-LRI supported project explores the hypothesis that chemical exposures during pregnancy can influence the immune system and development of allergy in children. Questionnaire data, as well as cord blood, plus blood and saliva samples at age 11 years, were collected in substudies of two longitudinal birth cohorts in Belgium (FLEHS1 & FLEHS2) and analyzed with Illumina Methylation 450K BeadChips as well as gene targeted iPLEX MassArrays analysis. The project aims to answer the following questions: 1) can we identify specific changes in epigenetic modifications on DNA from allergic compared to not-allergic children; 2) are these allergy-related epigenetic changes a result of chemical exposure during pregnancy; and 3) did the early life exposures leave an epigenetic “mark” that is maintained through childhood. If chemicals exposures and resulting predictive markers of allergic diseases can be detected early, prevention strategies, particularly in children or before pregnancy, could be developed.

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Associations between IFI44L gene variants and rates of respiratory tract infections during early childhood

Project description:Background: Genetic heterogeneity in the innate immune system may account for variable susceptibility to respiratory tract infections (RTIs) in children. Objective: We aimed to assess the impact of polymorphisms rs273259 and rs1333969 in type I interferon related gene IFI44L on susceptibility to RTIs and acute otitis media in children. Methods: In two prospective, population-based birth cohorts, the FinnBrain Birth Cohort Study and the STEPS Study, IFI44L genotypes for rs273259 and rs1333969 were determined in relation to the development of RTIs until one and two years of age, respectively, and adjusted incidence rate ratios (aIRR) or odds ratios (OR) were calculated. At age 3 months, whole blood transcriptional profiles were analyzed and nasal samples were tested for respiratory viruses in a subset of children. Results: In respiratory virus-positive children at 3 months of age, IFI44L gene variants were associated with decreased expression levels of IFI44L and several other interferon related genes. Conclusions: Variant forms of IFI44L gene were protective against early-childhood RTIs or acute otitis media in two independent birth cohorts, and they attenuated interferon pathway activation by respiratory viruses.

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Treg Cell TGF-β1 Regulates Distinct Checkpoints Governing Allergy and Autoimmunity

Project description:The mechanisms by which regulatory T (Treg) cells differentially control allergic and autoimmune responses remain unclear. We show that Treg cells in food allergy (FA) have decreased expression of transforming growth factor beta 1 (TGF-b1) due to IL-4 and STAT6-dependent inhibition of Tgfb1 transcription. These changes were modelled by Treg cell-specific Tgfb1 monoallelic inactivation, which induced allergic dysregulation by impairing microbiota-dependent ROR-gt+ Treg cell differentiation. This dysregulation was rescued by treatment with Clostridiales species, which upregulated Tgfb1 expression in Treg cells. Biallelic deficiency precipitated fatal autoimmunity, with intense autoantibody production and dysregulated T follicular helper and B cell responses. These results identify a privileged role for Treg cell-derived TGF-b1 in regulating allergy and autoimmunity at distinct checkpoints in a Tgfb1 gene dose and microbiota-dependent manner.

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Differential responses by human respiratory epithelial cell lines to respiratory syncytial virus reflect distinct patterns of infection control

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Project description:Allergy is one of the most common diseases among young children yet all factors that affect development of allergy remain unclear. In a small cohort of 65 children living in the same rural area of south-west Sweden, we have previously found that maternal factors, including prenatal diet, affect childhood allergy risk, suggesting that in utero conditions may be important for allergy development. Here, we studied if metabolites in the umbilical cord blood of newborns may be related to development of childhood allergy, accounting for key perinatal factors such as mode of delivery, birth order and sex. Umbilical cord blood plasma samples from 44 of the participants were analysed using gas chromatography-mass spectrometry metabolomics; allergy was diagnosed by specialised paediatricians at ages 18 months, 36 months and 8 years and included eczema, asthma, food allergy and allergic rhinoconjunctivitis. Nineteen cord blood metabolites were related to future allergy diagnosis though was no clear pattern of up- or downregulation of metabolic pathways. In contrast, perinatal factors birth order, sex and mode of delivery affected several energy and biosynthetic pathways, including glutamate and aspartic acid - histidine metabolism (p=0.004) and the tricarboxylic acid cycle (p=0.006) for birth order; branched chain amino acid metabolism (p=0.0009) and vitamin B6 metabolism (p=0.01) for sex; and glyoxylate and dicarboxylic acid metabolism (p=0.005) for mode of delivery. In conclusion, the cord blood metabolome includes individual metabolites that reflect lifestyle, microbial and other factors that may also be associated with future allergy diagnosis, and also reflects temporally close events/factors. Larger studies are required to confirm these associations, and perinatal factors such as birth order or siblings must be considered in future cord-blood metabolome studies.

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Childhood medulloblastoma

Project description:Childhood medulloblastoma

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