Abstract
BackgroundImmunological 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 (IL17A, IL17F, IL21, IL22 and IL26) and genes involved in differentiation (IL6, IL1B, TGFB1, IL23A and STAT3) and recruitment of Th17 cells (CCR6 and CCL20) 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 IL8 and TNF.ResultsEvaluation of mRNA expression levels in colonic and ileal control samples revealed that TNF, TGFB1, STAT3 and CCR6 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 IL17A, IL17F, IL21 and IL26 was detected in inflamed ileal samples, expression of the indispensable Th17 cell differentiation factors TGFB1 and IL23A, the signaling molecule STAT3 and the Th17 recruitment factors CCR6 and CCL20 were unchanged.ConclusionsOur findings suggest that immune regulation is different in colonic and ileal disease, which might have important consequences for therapeutic intervention.
Highlights
Immunological and genetic findings implicate Th17 effector cytokines in the pathogenesis of inflammatory bowel disease (IBD)
Crohn’s disease (CD) was believed to be mediated by Th1 cytokines, while ulcerative colitis (UC) was believed to be mediated by Th2 cytokines; recent data have implicated Th17 cells in the pathogenesis of IBD [5,6,7,8,9]
The invasion of extracellular bacteria into the intestinal mucosa triggers the expression of IL-23A, driving Th17 cells to release IL-17A, IL-17F, IL-21, IL-22 and IL-26, which in turn exert a number of proinflammatory effects on intestinal epithelial cells, endothelial cells, macrophages and fibroblasts [10]
Summary
Immunological and genetic findings implicate Th17 effector cytokines in the pathogenesis of inflammatory bowel disease (IBD). The invasion of extracellular bacteria into the intestinal mucosa triggers the expression of IL-23A, driving Th17 cells to release IL-17A, IL-17F, IL-21, IL-22 and IL-26, which in turn exert a number of proinflammatory effects on intestinal epithelial cells, endothelial cells, macrophages and fibroblasts [10]. In addition to their proinflammatory functions, IL-17A, IL-17F and IL-22 have been reported to induce increased expression of epithelial barrier protective genes such as defensins, mucins, tight junction proteins and lipopolysaccharide-binding proteins [11,12,13,14]
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