Expression of CXCR3 in human intestinal mucosa

RULLI E; ALLEGRETTI Y; BONDAR C; GUZMAN L; CUETO RUA E; DRUT E; CHIRDO F

Amsterdam

Congreso; 13th International Coeliac Disease Symposium; 2009

International Coeliac Disease Symposium

Interaction between gliadin and the intestinal epithelium results in increased permeability to macromolecules present in the gut lumen, leading to the activation of innate and, later, adaptive immunity. In coeliac disease (CD), early pathogenic events involve changes such as disruption of tight junction integrity and production of proinflammatory cytokines, such as IL-15, which plays a major role on this stage.  CXCR3 is a chemokine receptor, which interacts with CXCL10 (IP-10) among other ligands. Recently, it was reported that CXCR3 acts as a mucosal gliadin receptor and is responsible for gliadin-induced disruption of intestinal permeability. The aim of this study was to evaluate the expression of CXCR3 and to test different inducers of its expression in whole biopsies from paediatric CD patients and controls (as assessed by histology and serology). The expression of CXCR3, IFN-g and CXCL10 was analysed by Real-Time qPCR. CXCR3 inducibility was also investigated on THP-1 cells stimulated with the a-gliadin p31-43 peptide (known to trigger innate immunity mechanisms), IL-15, flagellin (TLR5 ligand), poly I:C (TLR3 ligand) and a combination of p31-43 and IL-15. As expected, the mucosal samples from CD patients showed a significant increase in IFN-g mRNA levels when compared to non-CD controls. The expression of CXCR3 and CXCL10 was found slightly, but not significantly, elevated in CD patients. Treatment of THP-1 cells with p31-43, IL-15, poly I:C or flagellin had no effect on the expression of CXCR3. Interestingly, a 4-fold increase in CXCR3 mRNA levels was observed when a combination of p31-43 and IL-15 was used to stimulate the cells.