Genetic variants of the IL22 promoter associate to onset of psoriasis before puberty and increased IL-22 production in T cells

J Invest Dermatol. 2014 Jun;134(6):1535-1541. doi: 10.1038/jid.2014.5. Epub 2013 Jan 3.


Most psoriasis susceptibility genes were identified in cohorts of mixed clinical phenotypes and the exploration of genes in clinical subtypes is scarce. IL-22 has an established role in host defense and in psoriasis skin pathology, reflecting the delicate balance between control of infection and immunopathology. In a case-control study, we compared the genetic association to IL22 in psoriasis onset in patients between 0-9 (n=207), 10-20 (n=394), and 21-40 (n=468) years with healthy controls (n=1,529). Logistic regression analysis revealed association to regulatory elements in the IL22 promoter confined to onset of psoriasis before puberty (odds ratio=1.45, P<0.0007). The associated variants contain putative binding sites for AhR, a potent inducer of IL-22 expression. In a luciferase assay, transcriptional activity of a high-risk gene variant resulted in 80% higher promoter activity (P=0.012) compared with a low-risk variant. Ex vivo stimulated T cells from peripheral blood were analyzed with flow cytometry. Children with psoriasis carrying a high-risk variant produced 1.7 times more IL-22 compared with low-risk variants (P=0.042). Our combined genetic and functional data support the notion that a genetic IL22 variant that promotes epithelial barrier defense is preferentially enriched in and may precipitate the onset of psoriasis at an early age.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Binding Sites
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Female
  • Gene Expression Regulation*
  • Genetic Variation
  • Genotype
  • Haplotypes
  • Humans
  • Infant
  • Infant, Newborn
  • Interleukins / genetics*
  • Male
  • Promoter Regions, Genetic*
  • Psoriasis / genetics*
  • Psoriasis / immunology
  • Receptors, Aryl Hydrocarbon / metabolism
  • Regression Analysis
  • Sequence Analysis, DNA
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism*
  • Young Adult


  • Interleukins
  • Receptors, Aryl Hydrocarbon
  • interleukin-22