title: Cord blood Tregs with stable FOXP3 expression are influenced by prenatal environment and associated with atopic dermatitis at the age of one year.
abstract: BACKGROUND
  Regulatory T cells (Tregs) with stable FOXP3 expression are characterized by a specific demethylated region in the FOXP3 gene (Treg-specific demethylated region, TSDR). The aim of this study was to analyse the influence of prenatal factors on cord blood Treg numbers, as detected by changes in the TSDR demethylation, and the subsequent risk for allergic diseases.
  
  
  METHODS
  Analyses were performed within the LINA study in blood samples from pregnant women (34th gestational week) and in cord blood (n = 346 mother-child pairs). Treg numbers were detected via DNA demethylation in the FOXP3 TSDR. At age 1, total and specific IgE was measured in children's blood. In addition, maternal cytokine production (Th1/Th2/Th17) was analysed. Exposure and disease outcomes were assessed by questionnaires.
  
  
  RESULTS
  Boys had lower Treg numbers compared with girls (P < 0.001). Parental atopy history, particularly maternal hay fever and paternal asthma were related to lower Treg numbers in cord blood (adj. MR = 0.81, 95% CI = 0.68-0.97; adj. MR = 0.60, 95% CI = 0.45-0.81). Maternal cytokines (IL-13, IL-17E and IFN-γ) and maternal smoking/exposure to tobacco smoke during pregnancy were also associated with decreased cord blood Treg numbers (adj. MR = 0.89, 95% CI = 0.97-1.00). Children with lower Treg numbers at birth had a higher risk to develop atopic dermatitis (adj. OR = 1.55, 95% CI = 1.00-2.41) and sensitization to food allergens (adj. OR = 1.55, 95% CI = 1.06-2.25) during the first year of life.
  
  
  CONCLUSIONS
  These results indicate that both genetic and environmental factors presumably influence the development of foetal Tregs. Low cord blood Treg numbers may predict early atopic dermatitis.
authors.affiliation: Department of Environmental Immunology, UFZ - Helmholtz Centre for Environmental Research Leipzig, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Hinz
authors.forename: M
authors.initials: M
authors.lastname: Bauer
authors.forename: S
authors.initials: S
authors.lastname: Röder
authors.forename: S
authors.initials: S
authors.lastname: Olek
authors.forename: J
authors.initials: J
authors.lastname: Huehn
authors.forename: U
authors.initials: U
authors.lastname: Sack
authors.forename: M
authors.initials: M
authors.lastname: Borte
authors.forename: J C
authors.initials: JC
authors.lastname: Simon
authors.forename: I
authors.initials: I
authors.lastname: Lehmann
authors.forename: G
authors.initials: G
authors.lastname: Herberth
mesh_terms: D015331:Cohort Studies; D016207:Cytokines / Q000097:blood; D019175:DNA Methylation; D003876:Dermatitis, Atopic / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics / Q000276:immunology*; D004781:Environmental Exposure; D005260:Female; D005312:Fetal Blood / Q000276:immunology*; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D005865:Gestational Age; D006801:Humans; D007223:Infant; D008297:Male; D018811:Maternal Exposure; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D011795:Surveys and Questionnaires; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
chemical_list: D016207:Cytokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse