Fetal mast cells mediate postnatal allergic responses dependent on maternal IgE.

Mast cells (MCs) are central effector cells in allergic reactions, often mediated by IgE. Allergies commonly start at an early age, and both MCs and IgE are detectable in fetuses. However, whether fetal MCs are functionally competent to IgE-mediated activation and the origin of fetal IgE are presently unknown. We show that human and mouse fetal MCs phenotypically mature through pregnancy and can be sensitized by maternal IgE. IgE crossed the placenta, dependent on the fetal neonatal Fc-receptor (FcRN), and sensitized fetal MCs for allergen-specific degranulation. Both passive and active prenatal sensitization conferred allergen sensitivity, resulting in postnatal skin and airway inflammation following the first allergen encounter. We report a role for MCs within the developing fetus and demonstrate that fetal MCs may contribute to antigen-specific vertical transmission of allergic disease.