Allergy risk is mediated by dendritic cells with congenital epigenetic changes.
One factor predisposing toward allergic responses is a maternal history of allergy. In a mouse model of maternal transmission of asthma risk, offspring of asthmatic, but not normal, mothers show increased allergic susceptibility, recreating epidemiologic observations in humans. Dendritic cells (DCs) capture and process antigens, and can skew immune responses toward a pro-allergic T helper 2 phenotype. Genome-wide analysis shows that neonates of allergic mothers are born with substantial changes in DNA methylation in their splenic CD11c(+) DCs, findings observed without any contact with allergens. We demonstrate that these DCs from allergen-naive neonates born to asthmatic mothers, but not DCs from offspring of normal mothers, confer increased allergic susceptibility to multiple allergens when adoptively transferred into normal recipient mice, manifesting as increased airway responsiveness and allergic inflammation. Other immune splenocytes, including macrophages and CD4+ T cells, did not transfer the effect. The "asthma-susceptible" DCs also show enhanced allergen-presentation activity in vitro. Our findings suggest that maternal allergy results in an altered epigenetic profile in neonatal DCs that is independent of encounters with allergens and is linked to pro-allergic function.
Fedulov
Alexey V
AV
Department of Environmental Health, Harvard School of Public Health, Boston, MA 02115, USA. afedulov@hsph.harvard.edu
Kobzik
Lester
L
D000818:Animals; D039521:CD11c Antigen / Q000096:biosynthesis; D016207:Cytokines / Q000378:metabolism; D019175:DNA Methylation; D003713:Dendritic Cells / Q000166:cytology*; D004195:Disease Models, Animal; D044127:Epigenesis, Genetic; D005260:Female; D005434:Flow Cytometry; D055106:Genome-Wide Association Study; D006801:Humans; D006967:Hypersensitivity / Q000235:genetics* / Q000276:immunology*; D008264:Macrophages / Q000166:cytology; D018811:Maternal Exposure; D051379:Mice; D011247:Pregnancy; D012306:Risk; D013154:Spleen / Q000166:cytology / Q000276:immunology
D039521:CD11c Antigen; D016207:Cytokines