P018 Role of CCL20-CCR6 axis and MMP9 in the mucosal inflammation and fibrosis in Inflammatory Bowel Disease
O. Inczefi*1, 2, T. Molnár1, A. Bálint1, R. Dainese3, M. Lévêque2, V. Bacquié2, C. Salvador-Cartier2, A. Rosztóczy1, R. Róka1, T. Piche3, V. Theodorou2, L. Ferrier2
1University of Szeged, 1st Department of Medicine, Szeged, Hungary, 2INRA TOXALIM , Neurogastrogastroenteorology and Nutrition Unit, Toulouse, France, 3CHU de Nice, Department of Gastroenterology, Nice, France
Inflammatory bowel diseases (IBD) are characterized by the activation of the innate immune system. Recent data suggest the alteration of the CCL20-CCR6 axis in IBD. Faecal matrix metalloprotease 9 (MMP9) was lately described as a valuable non-invasive biomarker of the disease activity. Our aims were to investigate the pathogenetic role of the C-C Chemokine ligand 20 (CCL20), human beta defensin 2 (hBD2)-Chemokine receptor 6 (CCR6) axis in the inflamed, fibrotic and healthy areas of the mucosa of the patients suffering from UC (ulcerative colitis), CD (Crohn's disease) or IBS (irritable bowel syndrome), and to observe the MMP9 expression pattern in these samples.
76 patients in 2 endoscopic centres were recruited. (Healthy: 29, CD: 25, UC: 14, IBS: 8) Mucosal biopsies were taken from inflamed, fibrotic and healthy area of the colon and inflamed or healthy ileum. QPCR analysis was performed to determine the CCL20 and MMP9 and hBD2 mRNA expression. Immunohistochemistry was performed from frozen colon samples of active ulcered CD or UC and inactive fibrotic CD or CU mucosal samples to analyze CCR6 receptor protein expression.
In healthy patients, ileal and colonic mRNA expression of CCL20 is not significantly different; hBD2 mRNA is not detectable; MMP9 mRNA is significantly (p=0,0018) more expressed in ileum compared to colon. In ileal samples both CCL20 and MMP9 are significantly more expressed in inflamed CD compared to the healthy subjects. There was no change in the colonic CCL20, hBD2 or MMP9 mRNA expression in the IBS patients compared to the control group. In CD or UC significantly higher mRNA expression of CCL20 and MMP9 were observed in inflamed mucosa than in macroscopically intact areas. The CCL20 expression is more prominent in the fibrotic zones than in the active ulcers, conversely, MMP9 mRNA expression is less intense in the fibrotic zones. HBD2 expression is just detectable in certain samples from acute mucosal inflammation and fibrotic areas. Regarding to CCR6 we found unique apical expression in the cryptal mucosal enterocytes. The receptor expression is down-regulated in ulcered lesions in CD, but not in UC samples and in the fibrotic areas both in CD and UC group.
Our study shows that hBD2-CCL20-CCR6 axis is involved in ileal and colonic inflammation and even in the scar formation in IBD. CCL20 axis is more active in fibrotic areas, which suggests it may play a role in fibrosis process. We found that MMP9 is more expressed in the normal ileum compared to colon, while elevated MMP9 mRNA level is linked to mucosal lesions in both UC and CD. CCR6 receptor expression profile is different in both diseases. Our data highlights the differences in the immunological process in CD and UC.