INVESTIGADORES
CHIRDO Fernando Gabriel
congresos y reuniones científicas
Título:
Analysis of the expression of inflammatory mediators (IL-15, IL-17, IL-23 and CXCL10) in intestinal mucosa of coeliac disease patients.
Autor/es:
BONDAR C; ALLEGRETTI Y; RULLI E; ARAYA R; GUZMAN L; CUETO RUA E; CHOPITA N; CHIRDO F
Lugar:
Amsterdam
Reunión:
Congreso; European Mucosal Immunology Group Meeting; 2010
Institución organizadora:
European Mucosal Immunology Group Meeting
Resumen:
The pa31-43 gliadin peptide induces different innate pathways which together with adaptive mechanisms lead to Coeliac Disease (CD) pathogenesis. Though IL-15 is one of the main cytokines in the early stages, gIFN is responsible for expansion and perpetuation of the mucosal damage. The aim of this work was to study the participation of IL-15, IL-23, gIFN pathways in CD pathogenesis. Expression of IL-15, IL-15Ra, gIFN, gIFNR, CXCR3, CXCL10, IL-17 and IL-23 was studied by Real-Time qPCR and by confocal fluorescence microscopy in intestinal biopsy samples from adult patients. Expression levels were also evaluated in biopsy samples (controls n=14, coeliac disease n=6) after incubation with pa31-43, IL-15 or both. Expression of IL-15, IL-15Ra and the number of IL-15+ cells were higher in active CD compared with controls. The expression of CXCL10 was also higher in active CD, Samples from control population grouped according to the level of IL-15Ra expression showed a positive correlation with the expression of CXCL10 and IFNgR. Strikingly, expression of CXCL10 was induced by IL-15 incubation in 8 out of 14 biopsies from controls. In active CD, this pathway was already fully upregulated in vivo.  Induction of CXCR3 was not observed in any biopsy samples but it was induced in Jurkat cells (model of T cells) incubated with IL-15. IL-17 expression as well as the number of IL-17+ cells and IL-23p19+ cells were higher in active CD than in controls. In conclusion, the IL-15, IL-23 and IL-17 axis are active in CD pathogenesis maintaining the dominant gIFN pattern. Some of those elements are also active in non-coeliac individuals suggesting that regulatory pathways must control the full activation of the inflammatory pathways.