CONICET | Buscador de Institutos y Recursos Humanos

Elements of both innate and adaptive immune response take part in the mucosal damage in active coeliac disease (CD). Incubation of intestinal biopsy samples with gliadin peptides (particularly, pa31-43) triggers different inflammatory pathways which lead to increase in intestinal permeability and induction of IL-15, among other effects. Though IL-15 is one of the key cytokines in the early stages of disease there is no a clear link with IL-23, IL-17 and gIFN production, which may initiate, expand and perpetuate the mucosal damage. The aim of this work was to evaluate the expression of CXCR3, CXCL10, IL-15, IL-15R, IL-17, IL-21, IL-23 by qPCR and/or fluorescence microscopy on intestinal biopsies samples of coeliac and control individuals from paediatric and adult population. By qPCR, expression of IL-17, IL-21 and CXCL10 was significantly higher in active CD compared with control samples. However, there was no difference for CXCR3. CXCL10 was higher in control biopsies stimulated with IL-15 and in coeliac samples incubated with IL-15 and pa31-43. IL-15Ra (RNAm) and the number of IL-15+ cells in intestinal mucosa were statistically higher in active CD. Control samples could be grouped according to the level of expression of IL-15R. Interestingly, samples with high IL-15R showed the higher expression of CXCL10. Strikingly, the location of IL-17+ or IL-23p19+ cells in intestinal mucosa was found different, suggesting different recruitment pathways. In conclusion, several inflammatory pathways are active in CD. IL-15, IL-17, IL-21, IL-23 and CXCL10 could participate in CD pathogenesis driving Th17 differentiation prior to or in parallel to the establishment of the dominant gIFN pattern. Some of those elements are also present in non-coeliac individuals suggesting that regulatory pathways must be active to preserve the homeostasis in healthy tissues.

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