Atopic dermatitis and skin diseaseIL10 polymorphisms influence neonatal immune responses, atopic dermatitis, and wheeze at age 3 years
Section snippets
Study population
Umbilical cord blood (n = 200; 72 samples from atopic mothers and 128 samples from nonatopic mothers) was obtained from neonates born in the Munich metropolitan area of Germany. Subjects were recruited from July 2005 to September 2007 during the last trimester of pregnancy (for details, see the Methods section in this article's Online Repository at www.jacionline.org). Our previous studies showed that maternal atopy negatively affects Treg cell quantity and function in cord blood.19, 20
Results
We assessed the genotype of 8 genetic variations in the IL10 gene (Table I) with a genotyping success rate of greater than 90%. On the basis of LD analyses, 4 major LD blocks were identified (Fig 1), each represented by a tagging SNP. Two tagging SNPs (rs1800890 and rs1878672) slightly deviated from HWE; however, they showed similar allele frequencies in comparison to the HapMap reference population Centre d'Etude du Polymorphisme Humain. In the following we focused on reporting immunologic
Discussion
In this study the effect of genetic variation in the IL10 gene on secretion of TH1/TH2 lineage and proinflammatory cytokines and expression of Treg cells was assessed in cord blood. Additionally, the potential role of IL10 SNPs on the development of immune-mediated diseases, such as AD or wheeze, until the age of 3 years was investigated. We detected a distinct pattern of T-cell lineage fate in carriers of IL10 polymorphisms in cord blood because they were primarily associated with decreased
References (49)
- et al.
The two faces of interleukin 10 in human infectious diseases
Lancet Infect Dis
(2006) - et al.
Interleukin-10 regulation in normal subjects and patients with asthma
J Allergy Clin Immunol
(1996) - et al.
Interleukin-10 promoter polymorphism in psoriasis
J Invest Dermatol
(2001) - et al.
Prenatal farm exposure is related to the expression of receptors of the innate immunity and to atopic sensitization in school-age children
J Allergy Clin Immunol
(2006) - et al.
Prenatal, perinatal, and heritable influences on cord blood immune responses
Ann Allergy Asthma Immunol
(2006) - et al.
Allergen-induced cytokine production, atopic disease, IgE, and wheeze in children
J Allergy Clin Immunol
(2003) - et al.
Cyclosporin A reduces CD4(+)CD25(+) regulatory T-cell numbers in patients with atopic dermatitis
J Allergy Clin Immunol
(2009) - et al.
Isolation of the human interleukin 10 promoter. Characterization of the promoter activity in Burkitt's lymphoma cell lines
Cytokine
(1995) - et al.
FOXP3 controls regulatory T cell function through cooperation with NFAT
Cell
(2006) - et al.
Genetic susceptibility to atopic dermatitis
Allergol Int
(2008)
Association of interleukin-10 gene promoter polymorphism in children with atopic dermatitis
J Pediatr
T(H)1 cells control themselves by producing interleukin-10
Nat Rev Immunol
Mechanisms of immune suppression by interleukin-10 and transforming growth factor-beta: the role of T regulatory cells
Immunology
Heterogeneity and plasticity of T helper cells
Cell Res
Interleukin-10-secreting type 1 regulatory T cells in rodents and humans
Immunol Rev
New insights into the molecular mechanism of interleukin-10-mediated immunosuppression
J Leukoc Biol
IL-10 inhibits cytokine production by activated macrophages
J Immunol
IL10 gene polymorphisms are associated with asthma phenotypes in children
Genet Epidemiol
Regulatory activity of autocrine IL-10 on dendritic cell functions
J Immunol
Functional characterization of human IL-10
Int Arch Allergy Immunol
Dust mite exposure modifies the effect of functional IL10 polymorphisms on allergy and asthma exacerbations
J Allergy Clin Immunol
Asthma and genes encoding components of the vitamin D pathway
Respir Res
Interleukin-10 promoter polymorphisms and atopic asthma in North Indians
Clin Exp Allergy
Novel single nucleotide polymorphisms in the distal IL-10 promoter affect IL-10 production and enhance the risk of systemic lupus erythematosus
J Immunol
Cited by (0)
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.
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.