CONICET | Buscador de Institutos y Recursos Humanos

Editorial on the Research TopicAddressing Roles for Glycans in Immunology Using Chemical BiologyIntroduction to Chemical GlycoimmunologyAdvances in genetic techniques have enabled the identification of disease-susceptibility genes and the development of experimental models for mechanistic studies. However, this progress has only partially translated into new therapies, highlighting the relevance of both epigenetic control of gene expression and post-translational modifications as control points in the transition from genotype to phenotype. The cell surface provides a tightly-regulated temporal and spatial signature containing crucial biological information, and much of its dynamic response to environmental factors remains to be explored.Glycoconjugates, macromolecules containing carbohydrates (glycans) linked to proteins or lipids, are a central component of the cell surface. These structurally diverse biomolecules expose their carbohydrate portion outside the cell, and in doing so, are essential in storing and transmitting information and regulating cell-cell interactions. One of the many fields where glycans have arisen as key communicators is immunology, as they mediate diverse immunological functions (Zhou et al., 2018). The complex mechanisms involved in the biosynthesis and assembly of glycans is a non-template driven manner, which results in a high, natural heterogeneity that is key to adapting cellular responses. However, structural characterization of these glycans and the functional interpretation of the array of carbohydrates on a cell surface, generally referred to as the glycome, remains an analytical challenge for chemists.Since the glycome is unique to each cell type and significantly different between organisms, "self" and "non-self" signals are imbedded in the glycome (Varki, 2011). Moreover, glycans on immune cells are involved in different processes such as cell differentiation, trafficking, and response to pathogens (Varki, 2017). In this sense, glycan information is translated by glycan binding proteins (GBPs), also called lectins. The abilities of these GBPs to modulate immune cell function is intimately connected to their ability to differentiate glycan structures in a precise and effective manner. Evolution of lectins has granted these proteins a selective recognition, which is influenced not only by structure, but also by multivalency of their cognate glycan ligand, reflecting the naturally crowded and heterogeneous state of the cell surface (Kaltner et al., 2019). Consequently, chemistry has been crucial in untangling the roles of GBP-glycan interactions. Chemical tools and approaches provide a powerful complementary approach that has greatly aided our understanding of GBPs by designing inhibitors and synthetic ligands able to control immune cell function via glycan recognition. Below, we discuss the 13 manuscripts within this series in the context of three themes: GBPs, immunomodulation, and technological advances.