IL10 polymorphisms influence neonatal immune responses, atopic dermatitis, and wheeze at age 3 years - 27/02/13
Corresponding author: Bianca Schaub, MD, University Children’s Hospital Munich, Lindwurmstr 4, 80337 Munich, Germany.Abstract |
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 TH1 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, TH2-skewed immune responses, and decreased IFN-γ 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 (R2 > 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]), TH1/TH2 cytokines, TNF-⍺, 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-⍺ and GM-CSF, and partially increased IFN-γ 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 TH1/TH2 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.
Le texte complet de cet article est disponible en PDF.Key words : Atopy, atopic dermatitis, cord blood, cytokines, IL-10, single nucleotide polymorphisms, regulatory T cells, wheeze
Abbreviations used : AD, CBMC, FOXP3, GITR, HWE, LAG3, LD, LpA, Ppg, SNP, TLR, Treg
Plan
| Supported by Bavarian Research Association PIZ-140-08 (to B.S.) and the German Research Foundation as part of the transregional collaborative research program TR22 “allergic immune responses of the lung,” grant DFG SFB TR22/A22 (to D.R. and B.S.). Further funding was provided by the Comprehensive Pulmonary Centre (CPC for B.S.) and by the German Ministry of Education and Research (BMBF) as part of the National Genome Research Network (NGFN), with grant NGFN 01GS0810 (to L.A.P. and M.K.). Genotyping was performed in collaboration with the Genome Analysis Centre of the Helmholtz Centre Munich. |
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| Disclosure of potential conflict of interest: E. von Mutius is a consultant for Novartis, GlaxoSmithKline, ALK-Abelló, and Protectimmun; has received speakers’ fees from InfectoPharm; has been supported by Airsonnett AB; is a member of the expert panel for the UK Research Excellence Framework; and is an Associate Editor of the Journal of Allergy and Clinical Immunology. M. Kabesch has financial interests in Roxall, GlaxoSmithKline, Novartis, Sanofi Aventis, Allergopharma, and AstraZeneca GmbH and has been supported by Deutsche Forschungsgemeinschaft (DFG), the BMBF, and the European Union (EU). B. Schaub has been supported by DFG and the EU. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 131 - N° 3
P. 789-796 - mars 2013 Retour au numéro
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