Regulation of TH17 markers early in life through maternal farm exposure

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:133

Article

Lluis, Anna¹  Ballenberger, Nikolaus¹  Illi, Sabina¹  Schieck, Maximilian²  Kabesch, Michael²  Illig, Thomas^3,4  Schleich, Isolde¹  von Mutius, Erika¹  Schaub, Bianca¹ 

[1] Ludwig Maximilians Univ Munchen, Univ Childrens Hosp Munich, Dept Pulm & Allergy, Munich, Germany

[2] Univ Childrens Hosp Regensburg KUNO, Dept Pediat Pneumol & Allergy, Regensburg, Germany

[3] Helmholtz Ctr Munich, Inst Epidemiol, Neuherberg, Germany

[4] Hannover Med Sch, Unified Biobank, Hannover, Germany

关键词: Cord blood;    cytokines;    farming;    innate;    single nucleotide polymorphism;    T(H)17 cells;    regulatory T cells;   

DOI  :  10.1016/j.jaci.2013.09.030

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

Free