Pregnant mothers provide their growing babies with everything they need to thrive: oxygen, nutrients and immune factors to protect the vulnerable fetus. As it turns out, mothers could also be unsuspectingly passing on other ‘unwanted’ attributes, like allergies.
Previously, scientists had found traces of immune cells known as mast cells as well as antibodies called immunoglobulin E (IgE) in mouse fetal tissues, both of which play key roles in allergic reactions. When exposed to an allergen, the body produces IgE, activating mast cells that release inflammatory molecules. However, little is known about the origins of fetal IgE and how exactly its presence influences the onset of allergies in infants.
To address these questions, Florent Ginhoux, Senior Principal Investigator at A*STAR’s Singapore Immunology Network (SIgN), along with collaborators Ashley St. John from Duke-NUS Medical School and Jerry Chan from KK Women’s and Children’s Hospital, used cellular and imaging techniques to characterize mast cells in fetal tissues and investigate their interactions with maternal IgE.
Through mouse models, they observed that maternal IgE produced in response to a specific allergen could transfer from pregnant mothers across the placenta and into the womb with the help of a receptor called FcRN.
Once bound to fetal mast cells, IgE triggered the immune cells to release their characteristic cocktail of chemicals, thereby activating the allergic response. Further studies revealed that maternal IgE also binds to human fetal mast cells, suggesting they can cross the placenta in humans in a similar manner.
Fascinatingly, they found that mouse pups born to mothers with specific allergies inherited these maternal sensitivities—resulting in constricted airways after a single exposure to the allergen. In contrast, adult mice typically require two allergen exposures before displaying a reaction.
“These pups had never seen the allergen in their life, but once exposed to pollen, they react immediately,” said Ginhoux. “The capacity to respond to the allergen was transferred from their mothers.”
Crucially, the developed sensitivities in the newborn mice were allergen-specific. While the pups whose mothers were allergic to pollen also reacted to ragweed, no adverse reactions were reported with dust mites, another common allergen.
For now, the team can only speculate what evolutionary advantage passing allergies on from mother to child could have. In follow-up studies, Ginhoux and the team plan to explore fundamental unknowns about the role of mast cells during embryonic development. “We want to understand how mast cells modulate the physiology of fetal organs and the long-term consequences of their activation by maternal IgE,” he concluded.
The A*STAR-affiliated researchers contributing to this research are from the Singapore Immunology Network (SIgN).
