Maternal asthma causes gene expression and epigenetic changes in neonatal dendritic cells

Abstract

In a mouse model of maternal transmission of asthma risk (J. Immunol 2003, 170:1683), baby mice of asthmatic (As), but not normal (Nrm), mothers show increased susceptibility to allergy. Adoptive transfer to normal baby mice of dendritic cells (DCs) harvested from asthma‐susceptible but allergen‐naïve neonates reproduces the increased susceptibility to asthma. To identify molecular mechanisms, we performed genomic and epigenomic profiling of neonatal DCs. 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 Nrm males. Splenic CD11c+ DCs of 14‐day old allergen‐naïve offspring from these As and Nrm mothers were isolated using magnetic beads. Gene expression profiles of total cell RNA were obtained using Illumina gene chip microarrays. Genomic DNA methylation wa profiled using Switchgear epigenomic chip arrays. We identified 30 genes with significantly different RNA expression, (0.5 – 2 fold). Analysis of epigenomic data identified up to 300 chromosomal regions with significantly different methylation status, (2 – 10 fold). Clustering methods and pathway analysis identified several interrelated gene groups that merit further study. Maternal asthma causes multiple significant gene expression and epigenetic changes in neonatal dendritic cells. ES 00002