Fetal mast cells mediate postnatal allergic responses dependent on maternal IgE

Abstract

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.

Microbial exposure during early human development primes fetal immune cells

“…that cross the placental barrier (Msallam et al, 2020). Interestingly, a recent report on plant development showed partial inheritance of plant microbiome by vertical transmission through seedling (Abdelfattah et al, 2021).…”

Reply

“…We thank Drs Honda and Kabashima for their thoughtful response 1 to our commentary on the study by Msallam et al 2 We recognize that mast cells (MCs) in fetal and neonatal skin display less FcεRI expression than those in the adult. Nonetheless, the study by Msallam et al 2 demonstrates that IgE transferred from dams passively sensitized with monomeric IgE directed against trinitrophenol (TNP) can be detected on cutaneous MCs in E17.5 pups in a dose-dependent manner.…”

Gestationally-Dependent Immune Organization at the Maternal-Fetal Interface

“…For example, mature α/β T cells emerge in humans at the end of the first trimester and only emerge in the final days of gestation in the mouse with the primary expansion of this subset occurring postnatally (Mold and McCune, 2012). Implantation and early placentation occur much earlier in gestation and the placenta continues to mature until birth (Li et al, 2020;McGrath et al, 2015;Msallam et al, 2020). Due to this timeline, fetal immune-cell characterization has largely been limited to the fetal body and, other than fetal macrophages, only maternal immune cells have been examined in the placenta.…”