title: Regulation of TH17 markers early in life through maternal farm exposure.
abstract: BACKGROUND
  Previous studies suggested that maternal farm exposure during pregnancy modulates early immune development toward an allergy-protective status potentially mediated by TH1 or regulatory T (Treg) cells. However, the underlying mechanisms might involve immune modulation of additional T-cell populations, such as TH17 cells, influenced by genetic predisposition.
  
  
  OBJECTIVE
  We examined the role of maternal farm exposure and genetic predisposition on TH17 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. TH17 lineage (retinoic acid receptor-related orphan receptor C [RORC], retinoic acid receptor-related orphan receptor α [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. TH17/Treg/TH1/TH2 cytokines and 7 single nucleotide polymorphisms within the TH17 lineage (RORC, IL23R, and IL17) were examined.
  
  
  RESULTS
  TH17 lineage mRNA markers were expressed at birth at low concentrations independent of maternal farm exposure. A positive correlation between TH17 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 TH17 lineage genes influenced gene expression of TH17 and Treg cell markers and cytokine secretion.
  
  
  CONCLUSIONS
  Gene expression of TH17 lineage markers in cord blood was not influenced by maternal farming. Yet TH17 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 TH17 immune maturation, potentially regulating the development of immune-mediated diseases, such as childhood asthma.
authors.affiliation: Department of Pulmonary and Allergy, University Children's Hospital Munich, LMU Munich, Munich, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Lluis
authors.affiliation: Department of Pulmonary and Allergy, University Children's Hospital Munich, LMU Munich, Munich, Germany.
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Ballenberger
authors.affiliation: Department of Pulmonary and Allergy, University Children's Hospital Munich, LMU Munich, Munich, Germany.
authors.forename: Sabina
authors.initials: S
authors.lastname: Illi
authors.affiliation: Department of Pediatric Pneumology and Allergy, University Children's Hospital Regensburg (KUNO), Regensburg, Germany.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Schieck
authors.affiliation: Department of Pediatric Pneumology and Allergy, University Children's Hospital Regensburg (KUNO), Regensburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Kabesch
authors.affiliation: Institute of Epidemiology, Helmholtz Centre Munich, Neuherberg, Germany; Unified Biobank, Hannover Medical School, Hannover, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Illig
authors.affiliation: Department of Pulmonary and Allergy, University Children's Hospital Munich, LMU Munich, Munich, Germany.
authors.forename: Isolde
authors.initials: I
authors.lastname: Schleich
authors.affiliation: Department of Pulmonary and Allergy, University Children's Hospital Munich, LMU Munich, Munich, Germany.
authors.forename: Erika
authors.initials: E
authors.lastname: von Mutius
authors.affiliation: Department of Pulmonary and Allergy, University Children's Hospital Munich, LMU Munich, Munich, Germany. Electronic address: Bianca.Schaub@med.uni-muenchen.de.
authors.forename: Bianca
authors.initials: B
authors.lastname: Schaub
mesh_terms: D000818:Animals; D000829:Animals, Domestic; D015415:Biomarkers; D004781:Environmental Exposure; D005260:Female; D005312:Fetal Blood / Q000276:immunology*; D051858:Forkhead Transcription Factors / Q000235:genetics; D006801:Humans; D006967:Hypersensitivity / Q000517:prevention & control; D018811:Maternal Exposure; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D012333:RNA, Messenger / Q000097:blood; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D015415:Biomarkers; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D012333:RNA, Messenger
keywords: Cord blood; T(H)17 cells; cytokines; farming; innate; regulatory T cells; single nucleotide polymorphism