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Role of the novel Th17 cytokine IL-17F in inflammatory bowel disease (IBD): Upregulated colonic IL-17F expression in active Crohn's disease and analysis of theIL17Fp.His161Arg polymorphism in IBD

Seiderer, Julia MD1; Elben, Ira1; Diegelmann, Julia MSc1; Glas, Jürgen MD, MSc1,2; Stallhofer, Johannes1; Tillack, Cornelia MD1; Pfennig, Simone1; Jürgens, Matthias1; Schmechel, Silke MSc1; Konrad, Astrid MD1; Göke, Burkhard MD1; Ochsenkühn, Thomas MD1; Müller-Myhsok, Bertram MD3; Lohse, Peter MD4; Brand, Stephan MD1,*

doi: 10.1002/ibd.20339
Original Basic Science Articles

Background: Interleukin (IL)-17F, produced in IL-23R-expressing Th17 cells, is a novel member of the IL-17 cytokine family. Given the association of IL23R with inflammatory bowel disease (IBD), we characterized the role of IL-17F in IBD including its intestinal gene expression and the effect of the IL17F p.His161Arg polymorphism on disease susceptibility and phenotype of Crohn's disease (CD) and ulcerative colitis (UC). In addition, we analyzed the IL17F p.His161Arg polymorphism for potential epistasis with IL23R and NOD2/CARD15 variants.

Methods: Intestinal IL-17F mRNA expression was measured by quantitative polymerase chain reaction (PCR). Genomic DNA from 1682 individuals (CD: n = 499; UC: n = 216; controls: n = 967) was analyzed for the presence of the IL17F p.His161Arg polymorphism, the 3 NOD2 variants, p.Arg702Trp, p.Gly908Arg, and p.Leu1007fsX1008, and 10 CD-associated IL23R variants.

Results: Intestinal IL-17F mRNA expression was 4.4-fold increased in inflamed colonic lesions compared to uninflamed biopsies in CD (P = 0.016) but not in UC. However, the mean intestinal IL-17F mRNA expression was higher in UC than in CD (P < 0.0001). The IL17F p.His161Arg substitution was observed with similar frequencies in IBD patients and controls and was not associated with a certain disease phenotype, but weakly associated with a low body mass index (BMI; P = 0.009) and an earlier age of disease onset (P = 0.039) in UC. There was no evidence for epistasis between the IL17F p.His161Arg polymorphism and IBD-associated single nucleotide polymorphisms within the IL23R gene.

Conclusions: Intestinal IL17F gene expression is increased in active CD. The IL17F p.His161Arg polymorphism is not associated with IBD susceptibility and has no epistatic interaction with CD-associated IL23R variants.

(Inclamm Bowel Dis 2007)

1Department of Medicine II-Grosshadern, University of Munich, Germany

2Department of Preventive Dentistry and Periodontology, University of Munich, Germany

3Max-Planck-Institute of Psychiatry, Munich, Germany

4Department of Clinical Chemistry-Grosshadern, University of Munich, Germany

* Department of Medicine II–Grosshadern, University of Munich, Marchioninistr. 15, D-81377 Munich, Germany (e-mail: stephan.brand@med.uni-muenchen.de)

Received 16 October 2007; Accepted 19 October 2007

Published online 18 December 2007 in Wiley InterScience (www.interscience.wiley.com).

Grant sponsor: University of Munich (Habilitationsstipendium); Grant sponsor: Robert Bosch Foundation; Grant sponsor: University of Munich (Promotionsstipendium); Grant sponsor: Deutsche Forschungsgemeinschaft; Grant Number: Br 1912/5-1; Grant sponsor: Else Kröner-Fresenius-Stiftung (Else Kröner Memorial Grant 2005; Grant Number: P50/05/EKMS05/62; Grant sponsor: Ludwig-Demling Grant 2007 from DCCV e.V.

The first 2 authors contributed equally to this work.

© Crohn's & Colitis Foundation of America, Inc.
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