Genetic predisposition for the development of allergic disease and exposure to allergens during childhood have been implicated as major determining factors for the development of asthma. However, increasing evidence suggests that the mother plays a unique and important role in influencing the development of fetal-infant immune responses to inhaled allergens, independent of genetic influences. The exact nature and mechanism of this maternal influence and how it might be associated with the development of allergic sensitization and asthma are not clear. Our preliminary studies indicate that offspring from ragweed (RW) sensitized (allergic) female beagle dogs develop serum RW-specific IgE and IgG, increased pulmonary resistance to inhaled RW or histamine challenge, increased lung eosinophilia, and increased mucus in the lung, whereas offspring from nonsensitized mothers do not. These results suggest that children from an asthmatic mother are exposed to a unique biological environment that may increase their risk for the development of asthma. We propose to test the hypothesis that elevated levels of maternal allergen specific factors and/or a Th2 skewed cytokine environment during pregnancy and/or early childhood are risk factors for the development of allergic sensitization and asthma in offspring from allergic mothers. Studies using RW-allergic and nonallergic beagle dogs will be utilized to address three working aims.
In Aim 1 we propose to test the hypothesis that maternal transmission of allergen-specific factors during pregnancy and/or nursing is a contributing factor in the development of allergic sensitization and asthma in offspring.
In Aim 2 we propose to test the hypothesis that a more Th2 skewed cytokine environment of an allergic mother leads to a Th2 immune bias in her offspring and this is associated with the subsequent development of allergic sensitization and asthma.
In Aim 3 we propose to test the hypothesis that there is a specific window of opportunity early after birth wherein the newborn from an allergic mother must be exposed to inhaled allergen in order for the maternal influence to translate into an asthmatic phenotype in the offspring. This application will provide new insight into the underlying mechanisms that contribute to the development of asthma and identify new targets for preventative therapies.
| Royer, Christopher M; Rudolph, Karin; Barrett, Edward G (2013) The neonatal susceptibility window for inhalant allergen sensitization in the atopically predisposed canine asthma model. Immunology 138:361-9 |
| Barrett, Edward G (2008) Maternal influence in the transmission of asthma susceptibility. Pulm Pharmacol Ther 21:474-84 |
