Maternal supplementation with α-tocopherol inhibits the development of offspring food allergy, H1R signaling and ultimately anaphylaxis early in life

Allison E Kosins, Haoran Gao, Ross L Blankenship, Lauren N Emmerson, Joel A Ochoa, Joan M Cook-Mills, The Journal of Immunology, Volume 214, Issue 2, February 2025, Pages 199–210, https://doi.org/10.1093/jimmun/vkae041

Abstract

Food allergy has had a rapid rise in prevalence, and thus it is important to identify approaches to limit the development of food allergy early in life. Because maternal dietary supplementation with α-tocopherol (α-T), an isoform of vitamin E, during pregnancy and nursing increases neonate plasma levels of α-T and can limit neonate development of other allergies, we hypothesized that α-T can limit development of food allergy. To assess this, male mice with mutations in their skin barrier genes (FT−/− mice) were mated with wild-type females that received a diet supplemented with α-tocopherol or a control diet. Starting at postnatal day 3, these FT+/− pups were sensitized 4 to 5 times over 2.5 weeks by skin co-exposure to the food allergen peanut extract (PNE) and the environmental allergen Alternaria alternata (Alt). Control pups were exposed to saline, PNE only or Alt only. Supplementation with α-T blocked Alt+PNE sensitization (anti-PNE-specific IgE), without blocking Alt+PNE-stimulated skin IL33, Areg, OSM, CCL11, TSLP or plasma MCPT1.

α-T reduced histamine receptor signaling in microvascular endothelial cells
 in vitro and VE-cadherin in vascular endothelial junctions in intestines in vivo

However, supplementation with α-T blocked mast cell activation, the increase in plasma histamine in Alt+PNE sensitized pups, histamine receptor stimulation of endothelial PKCα signaling, and ultimately oral PNE-induced anaphylaxis in Alt+PNE sensitized mice. Thus, maternal supplementation with α-tocopherol reduced development of food allergy and anaphylaxis in neonates. These results have implications for supplementation of mothers with α-tocopherol to limit development of food allergy in neonates with skin barrier mutations.

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