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

γ-Tocopherol supplementation of allergic female mice augments development of CD11c+CD11b+ dendritic cells in utero and allergic inflammation in neonates
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DOI:
10.1152/ajplung.00301.2015
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发表时间:
2016-04-15
影响因子:
4.9
通讯作者:
Cook-Mills, Joan M.
Cook-Mills, Joan M.
中科院分区:
医学2区
文献类型:
--
作者:
Abdala-Valencia, Hiam;Soveg, Frank;Cook-Mills, Joan M.

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γ-生育酚增加过敏性成年小鼠对过敏原攻击的反应,但不知道γ-生育酚是否调节过敏性疾病的发展。过敏性疾病的发展往往发生在生命的早期。在临床研究和动物模型中,过敏母亲的后代对过敏原攻击的反应性增加。因此,我们确定γ-生育酚是否会增加过敏雌性小鼠后代的过敏反应。过敏雌性小鼠在交配时开始补充γ-生育酚。来自过敏性母亲的幼仔产生了过敏性肺反应,而来自盐水处理母亲的幼仔对过敏原激发没有反应。过敏雌性小鼠补充γ-生育酚可使过敏原激发后幼仔支气管肺泡灌洗液和肺中嗜酸性粒细胞数量增加两倍。在幼鼠肺中,CD 11 c(+)树突状细胞的CD 11b(+)亚群和表达转录因子IRF 4的树突状细胞的数量也增加了约两倍。几种CD 11b(+)树突状细胞亚群无变化。此外,母体补充γ-生育酚可使子宫内胎肝CD 11b(+)CD 11 c(+)树突状细胞数量增加两倍。在幼鼠中,γ-生育酚增加了炎症介质CCL 11、双调蛋白、激活素A和IL-5的肺表达。总之,母体补充γ-生育酚增加了胎儿树突状细胞亚群的发育,这些亚群对过敏反应至关重要,并增加了过敏母亲的幼仔过敏反应的发展。这些结果对在产前维生素中补充γ-生育酚过敏的母亲有影响。
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.