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IL10 polymorphisms influence neonatal immune responses, atopic dermatitis, and wheeze at age 3 years.
J. Allergy Clin. Immunol. 131, 789-796 (2013)
Background: IL10 encodes for IL-10, an important anti-inflammatory cytokine with pleiotropic effects. It is crucial for development of immune tolerance, downregulates expression of T(H)1 cytokines, and is relevant for T-cell regulation. Several IL10 single nucleotide polymorphisms (SNPs) were associated with inflammatory diseases, such as atopic diseases, which might have their onset during early immune maturation. Objective: We hypothesized that IL10 SNPs are associated with decreased regulatory T (Treg) cell numbers, T(H)2-skewed immune responses, and decreased IFN-gamma levels in cord blood parallel with increased proinflammatory markers, subsequently leading to increased atopic diseases until 3 years. Methods: Eight genetic IL10 variants, represented by 4 linkage disequilibrium blocks (R-2 > 0.80) and 2 distal promoter SNPs, were genotyped in cord blood mononuclear cells of 200 healthy neonates. Cord blood mononuclear cells were cultured unstimulated or after stimulation with lipid A, peptidoglycan, PHA, house dust mite (Der p 1), or Der p 1 plus lipid A. mRNA expression of Treg cell-associated genes (forkhead box protein P3 [FOXP3], glucocorticoid-induced TNF receptor [GITR], lymphocyte activation gene 3 [LAG3]), T(H)1/T(H)2 cytokines, TNF-alpha, and GM-CSF were assessed. Atopic and respiratory outcomes (atopic dermatitis [AD] and wheeze) were assessed by means of questionnaire at age 3 years. Results: Carriers of 3 IL10 SNP blocks and both distal promoter SNPs showed reduced expression of Treg cell markers, reduced IL-5 levels, proinflammatory TNF-alpha and GM-CSF, and partially increased IFN-gamma levels. The same SNPs presented as determinant for AD, wheeze, or symptoms of AD, wheeze, or both at age 3 years. Conclusions: Polymorphisms in IL10 influenced Treg cell marker expression and T(H)1/T(H)2 and proinflammatory cytokine secretion early in life. This was relevant for further development of immune-mediated diseases, such as AD and wheeze, in early childhood.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Atopy ; Atopic Dermatitis ; Cord Blood ; Cytokines ; Il-10 ; Single Nucleotide Polymorphisms ; Regulatory T Cells ; Wheeze; Single-nucleotide Polymorphisms ; Interferon-gamma Production ; Gene Promoter Polymorphism ; Regulatory T-cells ; Interleukin-10 Promoter ; Cord Blood ; Cytokine Production ; Il-10 Production ; Asthma ; Children
ISSN (print) / ISBN 0091-6749
Quellenangaben Volume: 131, Issue: 3, Pages: 789-796
Publishing Place Amsterdam [u.a.]
Reviewing status Peer reviewed
Institute(s) Research Unit Molecular Epidemiology (AME)