Inflammatory Bowel Diseases in the Era of Glycomics

MARIÑO, KARINA

Gotemburgo

Simposio; Red científica de Glicociencias de la Universidad de Gotemburgo (GOThenburg GLYcosciences, GOTGLY; 2014

The Sahlgrenska Academy, University of Gothenburg, Suecia

Crohn disease and ulcerative colitis are chronic inflammatory intestinal diseases, often collectively referred as ?inflammatory bowel diseases? (IBD). Compelling evidence indicates a link between dysregulated Th1 and Th17 responses and IBD, and it has been speculated that a deficit in activated mucosal T-cell apoptosis contributes to the perpetuation of chronic intestinal inflammation by extending the life span of antigen-primed lymphocytes. In spite of the high incidence of these diseases, characterization of the molecular pathways involved in their onset and development is far from complete.In the postgenomic era, the study of the glycome (the whole repertoire of glycans in cells and tissues) has enabled the association of unique N- and O-glycan structures with specific physiological and pathological processes. Glycans are distinctively complex, but this feature is precisely what makes them compact units for delivery of specific and essential information. The task of deciphering the biological code encrypted by the ?glycome? is assigned to endogenous glycan-binding proteins or lectins, including C-type lectins, siglecs and galectins. Of particular interest Galectin-1 (Gal-1), a member of this family, acts a selective immunosuppressive agent by preferentially deleting pathogenic Th1 and Th17 cells and instructing the differentiation of tolerogenic dendritic cells. Its immunosuppressive function is mediated by the interaction with cell surface glycans. In this talk, we will present our recently obtained results, where we investigated how specific glycans (generated and/or modified during the transition from healthy to inflamed mucosa) could mediate cellular processes relevant to immune tolerance and inflammation in IBD. Using an interdisciplinary approach we studied changes in the expression profile of galectins and cell surface glycome of T lymphocytes during the development of intestinal inflammation. Our study includes not only experimental models of colitis, but also analysis of samples from a selected cohort of IBD patients. Considering the immunosuppressive activity of Gal-1, we focused our efforts into the study of this lectin and the ?Gal-1-associated glycome? (glyco-epitopes that are specific for Gal-1). These are the first steps into understanding the relevance of the galectin-glycan interactions in the onset and development of IBD, and we think they will contribute to a better knowledge of the immunopathological mechanisms underlying intestinal inflammation and to the development of novel therapeutic strategies.