Gunda Herberth1, Mario Bauer2, Michaela Gasch2, Denise Hinz2, Stefan Röder3, Sven Olek4, Tibor Kohajda5, Ulrike Rolle-Kampczyk5, Martin von Bergen6, Ulrich Sack7, Michael Borte8, Irina Lehmann9. 1. Department of Environmental Immunology, UFZ-Helmholtz Centre for Environmental Research Leipzig, Leipzig, Germany. Electronic address: gunda.herberth@ufz.de. 2. Department of Environmental Immunology, UFZ-Helmholtz Centre for Environmental Research Leipzig, Leipzig, Germany. 3. Core Facility Studies, UFZ-Helmholtz Centre for Environmental Research Leipzig, Leipzig, Germany. 4. Ivana Tuerbachova Laboratory for Epigenetics, Epiontis GmbH, Berlin, Germany. 5. Department of Metabolomics, UFZ-Helmholtz Centre for Environmental Research Leipzig, Leipzig, Germany. 6. Department of Metabolomics, UFZ-Helmholtz Centre for Environmental Research Leipzig, Leipzig, Germany; Department of Biotechnology, Chemistry and Environmental Engineering, Aalborg University, Aalborg, Denmark. 7. Institute for Clinical Immunology, University of Leipzig, Leipzig, Germany. 8. Children's Hospital, Municipal Hospital "St Georg," Academic Teaching Hospital of the University of Leipzig, Leipzig, Germany. 9. Department of Environmental Immunology, UFZ-Helmholtz Centre for Environmental Research Leipzig, Leipzig, Germany. Electronic address: irina.lehmann@ufz.de.
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.
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.
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