Maternal and cord blood miR-223 expression associates with prenatal tobacco smoke exposure and low regulatory T-cell numbers

doi:10.1016/j.jaci.2013.06.036

Journal of Allergy and Clinical Immunology

Volume 133, Issue 2, February 2014, Pages 543-550.e4

https://doi.org/10.1016/j.jaci.2013.06.036 Get rights and content

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.

Section snippets

Methods

For more detailed information, please see the Methods section in this article's Online Repository at www.jacionline.org.

Characteristics of the study population

Characteristics of the study population are listed in Table I. There were no differences in the distribution of considered parameters in the analyzed subcohort compared with the entire LINA cohort (Table I). Complete data, including miRNA analysis, cord blood Treg cell numbers, and VOC/metabolite measurements, were available from 441 children at birth and from 315 pregnant mothers (see Fig E1).

At the age of 1 year, 606 children had participated in the study, and 546 and 514 children

Discussion

In the present study we show for the first time that maternal tobacco smoke exposure during pregnancy associates with the blood expression level of miRNA-223, with an effect on children's cord blood Treg cell numbers and the subsequent allergy risk. We analyzed maternal blood during pregnancy and children's cord blood and demonstrate that both maternal and cord blood miRNA-223 expression were positively correlated with maternal urine cotinine levels. High miR-223 expression was associated with

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: The LINA study was supported by Helmholtz institutional funding (Helmholtz Centre for Environmental Research–UFZ).

: Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest.

^∗: These authors contributed equally to this work.

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Mechanisms of allergy and clinical immunologyMaternal and cord blood miR-223 expression associates with prenatal tobacco smoke exposure and low regulatory T-cell numbers

Background

Methods

Results

Conclusions

Section snippets

Methods

Characteristics of the study population

Discussion

Int J Hyg Environ Health

J Allergy Clin Immunol

Food Chem Toxicol

Toxicol Appl Pharmacol

Toxicology

Gastroenterology

Blood

Hum Immunol

Immunity

Maternal immune status in pregnancy is related to offspring's immune responses and atopy risk

Allergy

Cord blood cytokines are modulated by maternal farming activities and consumption of farm dairy products during pregnancy: the PASTURE Study

J Allergy Clin Immunol

Farm living: effects on childhood asthma and allergy

Nat Rev Immunol

Epigenetic regulation in murine offspring as a novel mechanism for transmaternal asthma protection induced by microbes

J Allergy Clin Immunol

The influence of maternal exposure to volatile organic compounds on the cytokine secretion profile of neonatal T cells

Environ Toxicol

T cell reactivity in neonates from an East and a West German city—results of the LISA study

Allergy

Cord blood Tregs with stable FOXP3 expression are influenced by prenatal environment and associated with atopic dermatitis at the age of one year

Allergy

450K epigenome-wide scan identifies differential DNA methylation in newborns related to maternal smoking during pregnancy

Environ Health Perspect

Cigarette smoking behaviors and time since quitting are associated with differential DNA methylation across the human genome

Hum Mol Genet

NF-kappaB inducing kinase, NIK mediates cigarette smoke/TNFalpha-induced histone acetylation and inflammation through differential activation of IKKs

PLoS One

Cigarette smoke exposure-associated alterations to non-coding RNA

Front Genet

Prenatal tobacco smoke exposure affects global and gene-specific DNA methylation

Am J Respir Crit Care Med

Downregulation of microRNA expression in the lungs of rats exposed to cigarette smoke

FASEB J

Mechanisms of allergy and clinical immunology
Maternal and cord blood miR-223 expression associates with prenatal tobacco smoke exposure and low regulatory T-cell numbers