title: IL10 polymorphisms influence neonatal immune responses, atopic dermatitis, and wheeze at age 3 years.
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 (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]), TH1/TH2 cytokines, TNF-α, 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-α 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.
authors.affiliation: University Children's Hospital Munich, Department of Pulmonary and Allergy, LMU Munich, Munich, Germany.
authors.forename: Diana
authors.initials: D
authors.lastname: Raedler
authors.forename: Sabina
authors.initials: S
authors.lastname: Illi
authors.forename: Leonardo Araujo
authors.initials: LA
authors.lastname: Pinto
authors.forename: Erika
authors.initials: E
authors.lastname: von Mutius
authors.forename: Thomas
authors.initials: T
authors.lastname: Illig
authors.forename: Michael
authors.initials: M
authors.lastname: Kabesch
authors.forename: Bianca
authors.initials: B
authors.lastname: Schaub
mesh_terms: D002675:Child, Preschool; D003876:Dermatitis, Atopic / Q000235:genetics* / Q000276:immunology; D005312:Fetal Blood / Q000276:immunology; D005838:Genotype; D006801:Humans; D007231:Infant, Newborn; D016753:Interleukin-10 / Q000235:genetics* / Q000276:immunology; D007963:Leukocytes, Mononuclear; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000378:metabolism; D012135:Respiratory Sounds / Q000235:genetics* / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
chemical_list: D012333:RNA, Messenger; D016753:Interleukin-10