Research Article

Fetal mast cells mediate postnatal allergic responses dependent on maternal IgE

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Science  20 Nov 2020:
Vol. 370, Issue 6519, pp. 941-950
DOI: 10.1126/science.aba0864

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Maternal IgE activates fetal mast cells

Mast cells (MCs) are immune cells that participate in allergic reactions through their activation by immunoglobulin E (IgE) antibodies. MCs arise early during mammalian development, but it is unclear whether IgE-mediated activation occurs in fetal tissues and what the source of IgE stimulation is. Msallam et al. show that human and mouse fetal MCs can be sensitized by IgE of maternal origin, which crosses the placental barrier through the fetal neonatal Fc receptor (see the Perspective by Rothenberg). Prenatal maternal sensitization conferred transient allergen sensitivity after birth and resulted in the development of postnatal skin and airway inflammation in the offspring after their first exposure to allergen. Thus, both maternal IgE and fetal MCs may influence mother-to-child transmission of allergic disease during gestation.

Science, this issue p. 941; see also p. 907


Mast cells (MCs) are central effector cells in allergic reactions that are often mediated by immunoglobulin E (IgE). Allergies commonly start at an early age, and both MCs and IgE are detectable in fetuses. However, the origin of fetal IgE and whether fetal MCs can degranulate in response to IgE-dependent activation are presently unknown. Here, 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 after 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.

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