Regulation of T(H)17 markers early in life through maternal farm exposure

Lluis, Anna and Ballenberger, Nikolaus and Illi, Sabina and Schieck, Maximilian and Kabesch, Michael and Illig, Thomas and Schleich, Isolde and von Mutius, Erika and Schaub, Bianca (2014) Regulation of T(H)17 markers early in life through maternal farm exposure. JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 133 (3). pp. 864-871. ISSN 0091-6749, 1097-6825

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Abstract

Background: Previous studies suggested that maternal farm exposure during pregnancy modulates early immune development toward an allergy-protective status potentially mediated by T(H)1 or regulatory T (Treg) cells. However, the underlying mechanisms might involve immune modulation of additional T-cell populations, such as T(H)17 cells, influenced by genetic predisposition. Objective: We examined the role of maternal farm exposure and genetic predisposition on T(H)17 cell responses to innate and adaptive immune stimulation in cord blood. Methods: Eighty-four pregnant mothers were recruited before delivery. Detailed questionnaires (60 nonfarming mother, 22 farming mothers, and 2 exclusions) assessed farming exposures. Cord blood was stimulated with lipid A, peptidoglycan (Ppg), or PHA. T(H)17 lineage (retinoic acid receptor-related orphan receptor C [RORC], retinoic acid receptor-related orphan receptor alpha [RORA], IL-23 receptor [IL23R], IL17, IL17F, and IL22) and Treg cell markers (forkhead box protein 3 [FOXP3], lymphocyte activation gene 3 [LAG3], and glucocorticoid-induced TNF receptor [GITR]) were assessed at the mRNA level. T(H)17/Treg/T(H)1/T(H)2 cytokines and 7 single nucleotide polymorphisms within the T(H)17 lineage (RORC, IL23R, and IL17) were examined. Results: T(H)17 lineage mRNA markers were expressed at birth at low concentrations independent of maternal farm exposure. A positive correlation between T(H)17 lineage markers and FOXP3 (mRNA) was observed on stimulation (nonfarming mothers: lipid A, Ppg, and PHA; farming mothers: Ppg and PHA), influenced by maternal farming. Specific single nucleotide polymorphisms within the T(H)17 lineage genes influenced gene expression of T(H)17 and Treg cell markers and cytokine secretion. Conclusions: Gene expression of T(H)17 lineage markers in cord blood was not influenced by maternal farming. Yet T(H)17 and Treg cell markers were positively correlated and influenced by maternal farm exposure. Our data suggest that prenatal exposures and genetic predisposition play a role during early T(H)17 immune maturation, potentially regulating the development of immune-mediated diseases, such as childhood asthma.

Item Type: Article
Uncontrolled Keywords: ROR-GAMMA-T; CHILDHOOD ASTHMA; CELL-DIFFERENTIATION; ATOPIC SENSITIZATION; MILK CONSUMPTION; RETINOIC ACID; MESSENGER-RNA; IGE LEVELS; IN-VIVO; ASSOCIATION; Cord blood; cytokines; farming; innate; single nucleotide polymorphism; T(H)17 cells; regulatory T cells
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Kinder- und Jugendmedizin
Depositing User: Dr. Gernot Deinzer
Date Deposited: 19 Nov 2019 13:59
Last Modified: 19 Nov 2019 13:59
URI: https://pred.uni-regensburg.de/id/eprint/10555

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