γ-Tocopherol supplementation of allergic female mice augments development of CD11c⁺CD11b⁺dendritic cells in utero and allergic inflammation in neonates

Abstract

γ-Tocopherol increases responses to allergen challenge in allergic adult mice, but it is not known whether γ-tocopherol regulates the development of allergic disease. Development of allergic disease often occurs early in life. In clinical studies and animal models, offspring of allergic mothers have increased responsiveness to allergen challenge. Therefore, we determined whether γ-tocopherol augments development of allergic responses in offspring of allergic female mice. Allergic female mice were supplemented with γ-tocopherol starting at mating. The pups from allergic mothers developed allergic lung responses, whereas pups from saline-treated mothers did not respond to allergen challenge. The γ-tocopherol supplementation of allergic female mice increased the numbers of eosinophils twofold in the pup bronchoalveolar lavage and lungs after allergen challenge. There was also about a twofold increase in pup lung CD11b(+) subsets of CD11c(+) dendritic cells and in numbers of these dendritic cells expressing the transcription factor IRF4. There was no change in several CD11b(-) dendritic cell subsets. Furthermore, maternal supplementation with γ-tocopherol increased the number of fetal liver CD11b(+)CD11c(+) dendritic cells twofold in utero. In the pups, γ-tocopherol increased lung expression of the inflammatory mediators CCL11, amphiregulin, activin A, and IL-5. In conclusion, maternal supplementation with γ-tocopherol increased fetal development of subsets of dendritic cells that are critical for allergic responses and increased development of allergic responses in pups from allergic mothers. These results have implications for supplementation of allergic mothers with γ-tocopherol in prenatal vitamins.

Mechanism for initiation of food allergy: Dependence on skin barrier mutations and environmental allergen costimulation

“…The risk for allergic disease in humans is associated with in utero and early exposures to environmental factors 5 . In animal studies, we and others have reported that offspring from allergic mothers are predisposed to allergic lung responses to suboptimal allergen doses 6–15 . It is not known whether offspring of allergic mother mice have increased responsiveness to sensitization to food allergens and food-induced anaphylaxis.…”

Oxidative Stress: Harms and Benefits for Human Health

“…In mice prone to allergic disease, supplementing allergic mothers (at the time of mating) with α -tocopherol was enough to inhibit the pup allergic responses [ 67 ], while γ -tocopherol supplementation amplified pup responses to allergens [ 70 ].…”

“…These differences in allergic response development exerted by α - or γ -tocopherol supplementation are dependent from their modulation of eosinophils and CD11c + CD11b + dendritic cell numbers in the lungs; α -tocopherol reduced both the cellular species, without affecting the number of CD11c + CD11b − regulatory dendritic cells, while γ -tocopherol increased both eosinophils and CD11c + CD11b + dendritic cells [ 69 , 70 ].…”

The Role of Vitamin E in Immunity

“…On the other hand, γ-tocopherol supplementation exerted an opposite response in the same model. In vivo supplementation of γ-tocopherol at 250 mg/kg diet in allergic female mice resulted in a higher number of lung eosinophils, a higher number of lung CD11c + CD11b + DCs, and higher levels of lung lavage CCL11 in the offspring [ 79 ].…”