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

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

Author information

1
Dermatology and Venereology Unit, Department of Medicine, Karolinska lnstitutet, Karolinska University Hospital, Stockholm, Sweden.
2
Ingrid Asp Psoriasis Research Center, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
3
Dermatology and Venereology Unit, Department of Medicine, Karolinska lnstitutet, Karolinska University Hospital, Stockholm, Sweden. Electronic address: mona.stahle@ki.se.

Abstract

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.

PMID:
24390134
DOI:
10.1038/jid.2014.5
[Indexed for MEDLINE]
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