Linking genetic susceptibility to Crohn's disease with Th17 cell function: IL-22 serum levels are increased in Crohn's disease and correlate with disease activity and IL23R genotype status

Inflamm Bowel Dis. 2008 Feb;14(2):204-12. doi: 10.1002/ibd.20315.


Background: We analyzed the influence of Crohn's disease (CD)-associated IL23R gene variants on IL-22 that is expressed in IL-23R+ Th17 cells.

Methods: IL-22 serum levels were measured in 242 CD patients and in 31 healthy controls. Subanalyses included serum levels of IL-6, TNF-alpha, IL-17A, IL-17F, C-reactive protein (CRP), and leukocyte count. In all patients, genotyping for 10 CD-associated IL23R single nucleotide polymorphisms (SNPs) and the 3 main CD-associated CARD15 variants was performed.

Results: There was a highly significant increase in IL-22 serum expression in CD patients compared to healthy controls (P = 2.53 x 10(-9)). IL-22 serum levels correlated with disease activity: IL-22 levels in patients with a Crohn's disease activity index (CDAI) >150 were significantly higher than in patients with a CDAI <150 (P = 0.001), while TNF-alpha and IL-6 were not significantly different between these 2 groups. Analyzing the effect of 10 IL23R variants on IL-22 serum levels, we demonstrated that the quotients of mean IL-22 serum levels of carriers of the minor allele to the mean serum IL-22 in wildtype carriers correlated highly with the corresponding CD susceptibility risk for each gene variant (r = 0.807). The IL-22 levels in carriers of CD risk-increasing IL23R variants were significantly higher than in carriers of CD risk-decreasing IL23R variants (P = 0.008).

Conclusions: The Th17 cytokine IL-22 is expressed at high levels in CD and correlates with disease activity, offering a better separation between active and inactive CD than IL-6 and TNF-alpha. IL23R genotypes influence IL-22 serum expression, linking genetic CD susceptibility to Th17 cell function for the first time.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biomarkers / blood
  • Case-Control Studies
  • Crohn Disease / genetics*
  • Crohn Disease / immunology
  • Female
  • Genetic Predisposition to Disease
  • Germany
  • Humans
  • Interleukins / blood*
  • Male
  • Middle Aged
  • Nod2 Signaling Adaptor Protein / genetics
  • Polymorphism, Single Nucleotide*
  • Receptors, Interleukin / genetics*
  • Receptors, Interleukin / immunology
  • T-Lymphocytes, Helper-Inducer / immunology*
  • White People / genetics


  • Biomarkers
  • IL23R protein, human
  • Interleukins
  • Nod2 Signaling Adaptor Protein
  • Receptors, Interleukin
  • interleukin-22