[Speaker] Santiago P. Mendez Huergo:1
[Co-author] Gabriel A. Rabinovich:1,2
1:Laboratory of Immunopathology, Institute of Biology and Experimental Medicine, CONICET, Buenos Aires, Argentina, 2:School of Exact and Natural Sciences, University of Buenos Aires, Buenos Aires, Argentina

In the postgenomic era, the study of the glycome- the whole repertoire of saccharides in cells and tissues- has enabled the association of unique glycan structures with specific physiological and pathological processes. The responsibility for deciphering this biological information is assigned to endogenous glycan-binding proteins or lectins whose expression is regulated at sites of inflammation, infection and tumor growth. Galectins, a family of highly conserved glycan-binding proteins, control immune and vascular signaling programs by modulating reorganization, clustering and signaling threshold of relevant glycosylated receptors. Our laboratory investigates the molecular interactions between endogenous galectins and glycans leading to the control of immune tolerance and homeostasis. In the past years, we identified essential roles for galectin-1 (Gal-1), a proto-type member of this family, in tolerogenic circuits operating during tumor growth, microbial invasion and resolution of inflammation associated to autoimmune and allergic disorders, neurodegeneration, pregnancy and cardiovascular diseases. Mechanistically, this endogenous lectin acts by selectively dampening Th1 and Th17 responses, instructing the differentiation of tolerogenic dendritic cells, promoting the expansion of regulatory T cells, favoring M2 macrophage polarization and modulating eosinophil trafficking. We have shown in several models of autoimmunity and inflammation, including experimental autoimmune encephalomyelitis, collagen-induced arthritis, experimental autoimmune uveitis, TNBS-induced colitis and experimental autoimmune orchitis, that Gal-1 treatment attenuates the clinical severity of the disease, suggesting a therapeutic potential for this glycan-binding protein. Moreover, our studies identified a glycosylation-dependent, Gal-1-mediated program that links tumor hypoxia, immunosuppression and vascularization and hinders success of anti-angiogenic and immunotherapeutic modalities. In conclusion, our studies contributed to elucidate novel pathways via which endogenous galectins translate glycan-encoded information into unique signaling programs, findings that bring unifying principles to the diverse fields of immune regulation, oncology, autoimmunity and vascular biology. These observations have opened new possibilities for development of therapeutic strategies aimed at potentiating antitumor responses, reinforcing antimicrobial immunity and limiting autoimmune inflammation.
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