485 Mast cells in neonatal skin are functionally immature and hardly sensitized with IgE

Abstract

Mast cells (MCs) are innate immune cells residing in various organs including skin. MCs capture Immunoglobulin E (IgE) through high-affinity IgE receptors (FceRI). Upon binding to cognate antigen, cross-linking of FceRI bound by IgE occurs, leading to the degranulation of MCs and the development of type I hypersensitivity. Previous studies reported the existence of IgE in umbilical cord blood, suggesting a possibility that maternal IgE is transplacentally transported to neonates, and may cause type I hypersensitivity in neonates similar to the pathology in neonatal lupus, in which pathogenic maternal IgG is transplacentally transported to neonates and causes various organ involvement. However, neonates rarely develop type I hypersensitivity, even born from allergic mothers with high levels of serum IgE, suggesting that MCs in neonates may be functionally different from MCs in adult. Here, we investigated the transplacental transfer of IgE and the functional characteristics of MCs in neonatal skin. First, to confirm the transplacental transfer of IgE, we injected IgE to pregnant mice intravenously, then analyzed serum levels of IgE in fetuses by Enzyme-Linked ImmunoSorbent Assay. Although IgE was not detected in fetal sera in monomeric form, it was detected in fetal sera in the form of IgE/anti-IgE IgG immune complexes (ICs). The ICs induced degranulation of MCs in adult skin in the presence of cognate antigen, while they did not induce degranulation of MCs in neonatal skin. Compared with MCs in adult skin, MCs in neonates exhibited significantly impaired expression levels of FceRI. Consistently, only a small fraction of neonatal MCs capture IgE on their surface, while almost all MCs capture IgE in adult skin. MCs in the skin of human neonates also exhibited significantly impaired expression of FceRI. Taken together, our results suggest that MCs in neonatal skin are functionally immature and fail to elicit type I hypersensitivity in spite of the maternal transfer of IgE.