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

摘要

gamma-Tocopherol increases responses to allergen challenge in allergic adult mice, but it is not known whether gamma-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 gamma-tocopherol augments development of allergic responses in offspring of allergic female mice. Allergic female mice were supplemented with gamma-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 gamma-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 gamma-tocopherol increased the number of fetal liver CD11b~+CD11c~+ dendritic cells twofold in utero. In the pups, gamma-tocopherol increased lung expression of the inflammatory mediators CCL11, amphiregulin, activin A, and IL-5. In conclusion, maternal supplementation with gamma-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 gamma-tocopherol in prenatal vitamins.