Maternal exposure to diesel exhaust particles alters neonatal dendritic cell DNA methylation profiles and skews function towards pro-Th2 responses. (141.13)

Abstract

Abstract Neonates of mother mice exposed to allergen are born with increased risk of allergy; their dendritic cells (DC) carry the increased risk phenotype when transferred into normal recipients. These ‘pro-allergic’ DCs have vastly altered DNA methylation profiles. We investigated if epigenetic changes and ‘pro-allergic’ skewing also exist in DCs from offspring of mothers exposed during pregnancy to a pollutant linked to Th2 polarization, diesel exhaust particles (DEP). METHODS: Purified splenic CD11c+ DC of 14-d.o. allergen-naïve offspring from DEP-exposed or vehicle control mothers (n=6/group), as well as from positive control neonates born to OVA-sensitized and challenged females (n=3) were adoptively transferred to 3-d.o. recipients (n=12/group), followed by a low-dose OVA protocol which does not induce responses in normal controls. DCs were also screened for genome-wide DNA methylation changes. RESULTS: Recipients of DCs from neonate donors born to DEP-exposed mothers, but not to vehicle controls, revealed increased airway responsiveness and increased lung eosinophilia, which was similar in magnitude to recipients of DC from neonates born to asthma mothers. DNA methylation testing revealed shared patterns of epigenetic alterations in the DCs from DEP and asthma groups not seen in controls. CONCLUSION: Pregnancy exposure to DEP leads to ‘pro-allergic’ skew in neonatal DC; shared DNA methylation alterations suggest epigenetic involvement in increased allergy risk.