title: Maternal and cord blood miR-223 expression associates with prenatal tobacco smoke exposure and low regulatory T-cell numbers.
abstract: BACKGROUND
  There is evidence that microRNAs (miRNAs) are sensitive to environmental stressors, including tobacco smoke. On the other hand, miRNAs are involved in immune regulation, such as regulatory T (Treg) cell differentiation. The aim of the present study was to investigate the association between prenatal tobacco smoke exposure, miRNAs, and Treg cell numbers.
  
  
  METHODS
  Within a prospective mother-child study (Lifestyle and Environmental Factors and Their Influence on Newborns Allergy Risk), we analyzed the expression of miR-155 and miR-223 together with Treg cell numbers in maternal blood during pregnancy, as well as in cord blood (n = 441). Tobacco smoke exposure was assessed based on questionnaire answers and maternal urine cotinine levels. Additionally, the concentration of smoking-related volatile organic compounds was measured in dwellings of study participants.
  
  
  RESULTS
  Both maternal and cord blood miR-223 expressions were positively correlated with maternal urine cotinine levels. An association was also found between maternal miR-223 expression and indoor concentrations of benzene and toluene. High miR-223 expression was associated with lower Treg cell numbers in maternal and cord blood. Furthermore, children with lower Treg cell numbers at birth had a higher risk of atopic dermatitis during the first 3 years of life. The concentration of the toluene metabolite S-benzylmercapturic acid in maternal urine was associated with decreased cord blood, but not maternal blood, miR-155 expression. A relationship between miR-155 expression and Treg cell numbers was not found.
  
  
  CONCLUSIONS
  For the first time, we show that maternal tobacco smoke exposure during pregnancy correlates with the level of miRNA-223 expression in blood, with an effect on children's cord blood Treg cell numbers and subsequent allergy risk.
authors: Department of Environmental Immunology, UFZ-Helmholtz Centre for Environmental Research Leipzig, Leipzig, Germany. Electronic address: gunda.herberth@ufz.de.
authors: Gunda
authors: G
authors: Herberth
authors: Department of Environmental Immunology, UFZ-Helmholtz Centre for Environmental Research Leipzig, Leipzig, Germany.
authors: Mario
authors: M
authors: Bauer
authors: Department of Environmental Immunology, UFZ-Helmholtz Centre for Environmental Research Leipzig, Leipzig, Germany.
authors: Michaela
authors: M
authors: Gasch
authors: Department of Environmental Immunology, UFZ-Helmholtz Centre for Environmental Research Leipzig, Leipzig, Germany.
authors: Denise
authors: D
authors: Hinz
authors: Core Facility Studies, UFZ-Helmholtz Centre for Environmental Research Leipzig, Leipzig, Germany.
authors: Stefan
authors: S
authors: Röder
authors: Ivana Tuerbachova Laboratory for Epigenetics, Epiontis GmbH, Berlin, Germany.
authors: Sven
authors: S
authors: Olek
authors: Department of Metabolomics, UFZ-Helmholtz Centre for Environmental Research Leipzig, Leipzig, Germany.
authors: Tibor
authors: T
authors: Kohajda
authors: Department of Metabolomics, UFZ-Helmholtz Centre for Environmental Research Leipzig, Leipzig, Germany.
authors: Ulrike
authors: U
authors: Rolle-Kampczyk
authors: Department of Metabolomics, UFZ-Helmholtz Centre for Environmental Research Leipzig, Leipzig, Germany; Department of Biotechnology, Chemistry and Environmental Engineering, Aalborg University, Aalborg, Denmark.
authors: Martin
authors: M
authors: von Bergen
authors: Institute for Clinical Immunology, University of Leipzig, Leipzig, Germany.
authors: Ulrich
authors: U
authors: Sack
authors: Children's Hospital, Municipal Hospital "St Georg," Academic Teaching Hospital of the University of Leipzig, Leipzig, Germany.
authors: Michael
authors: M
authors: Borte
authors: Department of Environmental Immunology, UFZ-Helmholtz Centre for Environmental Research Leipzig, Leipzig, Germany. Electronic address: irina.lehmann@ufz.de.
authors: Irina
authors: I
authors: Lehmann
mesh_terms: D016902:Air Pollution, Indoor / Q000032:analysis; D001555:Benzene Derivatives / Q000032:analysis; D018791:CD4 Lymphocyte Count; D002675:Child, Preschool; D003876:Dermatitis, Atopic / Q000175:diagnosis / Q000276:immunology*; D005260:Female; D005312:Fetal Blood / Q000276:immunology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D018811:Maternal Exposure; D008431:Maternal-Fetal Exchange / Q000276:immunology*; D035683:MicroRNAs / Q000097:blood* / Q000276:immunology; D011247:Pregnancy / Q000276:immunology*; D012907:Smoking; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*; D014028:Tobacco Smoke Pollution
chemical_list: D001555:Benzene Derivatives; D035683:MicroRNAs; D014028:Tobacco Smoke Pollution; C525067:MIR223, human
keywords: ETS; Effector T; Environmental tobacco smoke; FOXP3; Forkhead box protein 3; Genomic DNA; LINA; Lifestyle and Environmental Factors and Their Influence on Newborns Allergy Risk; MR; Mean ratio; MicroRNA; RT; Regulatory T; Reverse transcription; S-benzylmercapturic acid; S-phenylmercapturic acid; SBMA; SPMA; TSDR; Teff; Treg; Treg cell–specific demethylated region; VOC; Volatile organic compound; cord blood; gDNA; miR-155; miR-223; miRNA; pregnancy; regulatory T cells; tobacco smoke