title: α-Tocopherol supplementation of allergic female mice inhibits development of CD11c+CD11b+ dendritic cells in utero and allergic inflammation in neonates.
abstract: α-Tocopherol blocks responses to allergen challenge in allergic adult mice, but it is not known whether α-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 α-tocopherol blocked development of allergic responses in offspring of allergic female mice. Allergic female mice were supplemented with α-tocopherol starting at mating. The pups from allergic mothers developed allergic lung responses, whereas pups from saline-treated mothers did not respond to the allergen challenge, and α-tocopherol supplementation of allergic female mice resulted in a dose-dependent reduction in eosinophils in the pup bronchoalveolar lavage and lungs after allergen challenge. There was also a reduction in pup lung CD11b(+) dendritic cell subsets that are critical to development of allergic responses, but there was no change in several CD11b(-) dendritic cell subsets. Furthermore, maternal supplementation with α-tocopherol reduced the number of fetal liver CD11b(+) dendritic cells in utero. In the pups, there was reduced allergen-induced lung mRNA expression of IL-4, IL-33, TSLP, CCL11, and CCL24. Cross-fostering pups at the time of birth demonstrated that α-tocopherol had a regulatory function in utero. In conclusion, maternal supplementation with α-tocopherol reduced fetal development of subsets of dendritic cells that are critical for allergic responses and reduced development of allergic responses in pups from allergic mothers. These results have implications for supplementation of allergic mothers with α-tocopherol.
authors.affiliation: Allergy-Immunology Division, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Hiam
authors.initials: H
authors.lastname: Abdala-Valencia
authors.affiliation: Allergy-Immunology Division, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Sergejs
authors.initials: S
authors.lastname: Berdnikovs
authors.affiliation: Allergy-Immunology Division, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Frank W
authors.initials: FW
authors.lastname: Soveg
authors.affiliation: Allergy-Immunology Division, Northwestern University Feinberg School of Medicine, Chicago, Illinois j-cook-mills@northwestern.edu.
authors.forename: Joan M
authors.initials: JM
authors.lastname: Cook-Mills
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000494:pharmacology*; D039481:CD11b Antigen / Q000276:immunology*; D039521:CD11c Antigen / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D019587:Dietary Supplements; D005260:Female; D006967:Hypersensitivity / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D051379:Mice; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D024502:alpha-Tocopherol / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D039481:CD11b Antigen; D039521:CD11c Antigen; D016207:Cytokines; D024502:alpha-Tocopherol
keywords: allergic lung inflammation; vitamin E