It Takes Two to Tango: Mapping Galectin-1-Glycan Interactions in the Quest for Novel Therapeutic Strategies in IBD

MARIÑO, KARINA VALERIA; RABINOVICH, GABRIEL A.

San Francisco, USA

Conferencia; Kenneth Rainin Foundation Innovations Symposium; 2018

Kenneth Rainin Foundation

Galectin-1 (Gal1), a carbohydrate-binding protein, can exert protective and immunomodulatory activity in models of inflammatory diseases. The mechanisms underlying the anti-inflammatory effects of Gal1 are complex and include control of effector T cell survival, cytokine balance, and generation of tolerogenic dendritic cells. Our results show that an altered glycosylation influences development and resolution of intestinal inflammation, as shown in C2GnT1 mice. The significance of this aberrant O-glycome in experimental models is validated by the decreased C2GNT1 expression in the human disease. On the other hand, Galectin-1, an immunomodulatory lectin, is increased both in the TNBS model of colitis and in IBD patient biopsies, but not at a systemic level, suggesting that this lectin is part of a complex network of resolution mechanisms in the gut. In spite of increased Gal1 levels, its immunoregulatory role may be compromised by the inflammatory microenvironment, as administration of resistant Gal1 variants has an improved immunomodulatory effect. In summary, the Gal1-glycan axis emerges as a synchronized program that controls intestinal inflammation which we are only starting to understand.