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An exposome perspective: Early-life events and immune development in a changing world

Here we review the historical origins of exposome research and define a new concept, the metaexposome

Vitamin D over the first decade and susceptibility to childhood allergy and asthma

We aimed to research relationships between 25(OH)D levels from birth to 10 y/o and susceptibility to allergic sensitization, respiratory issues and asthma.

Rare variant analysis in eczema identifies exonic variants in DUSP1, NOTCH4 and SLC9A4

Previous genome-wide association studies revealed multiple common variants involved in eczema but the role of rare variants remains to be elucidated. Here, we investigate the role of rare variants in eczema susceptibility. We meta-analyze 21 study populations including 20,016 eczema cases and 380,433 controls. Rare variants are imputed with high accuracy using large population-based reference panels.

Innate Immune Training for Prevention of Recurrent Wheeze in Early Childhood

Pat Deborah Holt Strickland PhD, DSc, FRCPath, FRCPI, FAA PhD Emeritus Honorary Researcher Head, Pregnancy and Early Life Immunology Patrick.Holt@

IRF7-Associated Immunophenotypes Have Dichotomous Responses to Virus/Allergen Coexposure and OM-85-Induced Reprogramming

High risk for virus-induced asthma exacerbations in children is associated with an IRF7lo immunophenotype, but the underlying mechanisms are unclear. Here, we applied a Systems Biology approach to an animal model comprising rat strains manifesting high versus low susceptibility to experimental asthma, induced by virus/allergen coexposure, to elucidate the mechanism(s)-of-action of the high-risk asthma immunophenotype.

Protection against neonatal respiratory viral infection via maternal treatment during pregnancy with the benign immune training agent OM-85

Incomplete maturation of immune regulatory functions at birth is antecedent to the heightened risk for severe respiratory infections during infancy. Our forerunner animal model studies demonstrated that maternal treatment with the microbial-derived immune training agent OM-85 during pregnancy promotes accelerated postnatal maturation of mechanisms that regulate inflammatory processes in the offspring airways.

Transplacental immune modulation with a bacterial-derived agent protects against allergic airway inflammation

These data provide proof of concept supporting the rationale for developing transplacental immune reprogramming approaches for primary disease prevention

Trajectories of childhood immune development and respiratory health relevant to asthma and allergy

Our findings demonstrate the utility of unsupervised analysis in elucidating heterogeneity in asthma pathogenesis

Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis

GWAS analyses of allergic sensitization against inhalant allergens and nonallergic rhinitis suggested shared genetic mechanisms across rhinitis-related traits

Persistent activation of interlinked type 2 airway epithelial gene networks in sputum-derived cells from aeroallergen-sensitized symptomatic asthmatics

Our findings provide new insight into the molecular mechanisms operative at baseline in the airway mucosa in atopic asthmatic with natural aeroallergen exposure