Differential mucosal expression of Th17-related genes between the inflamed colon and ileum of patients with inflammatory bowel disease

oleh: Verbruggen Gust, Boon Nico, Olievier Kim, Melis Lode, Peeters Harald, Laukens Debby, Bogaert Sara, Vandesompele Jo, Elewaut Dirk, De Vos Martine

Format: Article
Diterbitkan: BMC 2010-12-01

Deskripsi

<p>Abstract</p> <p>Background</p> <p>Immunological and genetic findings implicate Th17 effector cytokines in the pathogenesis of inflammatory bowel disease (IBD). Expression of Th17 pathway-associated genes is mainly studied in colonic disease. The present study assessed the mRNA expression levels of Th17 effector cytokines (<it>IL17A</it>, <it>IL17F</it>, <it>IL21</it>, <it>IL22 </it>and <it>IL26</it>) and genes involved in differentiation (<it>IL6</it>, <it>IL1B</it>, <it>TGFB1</it>, <it>IL23A </it>and <it>STAT3</it>) and recruitment of Th17 cells (<it>CCR6 </it>and <it>CCL20</it>) by quantitative real-time PCR analysis of colonic and ileal biopsies from 22 healthy control subjects, 26 patients with Crohn's disease (CD) and 12 patients with ulcerative colitis (UC). Inflammation was quantified by measuring expression of the inflammatory mediators <it>IL8 </it>and <it>TNF</it>.</p> <p>Results</p> <p>Evaluation of mRNA expression levels in colonic and ileal control samples revealed that <it>TNF</it>, <it>TGFB1</it>, <it>STAT3 </it>and <it>CCR6 </it>were expressed at higher levels in the ileum than in the colon. Expression of all the Th17 pathway-associated genes was increased in inflamed colonic samples. The increased expression of these genes was predominantly observed in samples from UC patients and was associated with more intense inflammation. Although increased expression of <it>IL17A</it>, <it>IL17F</it>, <it>IL21 </it>and <it>IL26 </it>was detected in inflamed ileal samples, expression of the indispensable Th17 cell differentiation factors <it>TGFB1 </it>and <it>IL23A</it>, the signaling molecule <it>STAT3 </it>and the Th17 recruitment factors <it>CCR6 </it>and <it>CCL20 </it>were unchanged.</p> <p>Conclusions</p> <p>Our findings suggest that immune regulation is different in colonic and ileal disease, which might have important consequences for therapeutic intervention.</p>