Addressing Roles for Glycans in Immunology using Chemical Biology

Glycoconjugates, macromolecules containing carbohydrates (glycans) conjugated to proteins or lipids, are a diverse class of biopolymers capable of regulating cell-cell interactions. They are present in a high, natural heterogeneity, which originates from the complex mechanisms involved in their biosynthesis. Genetic and environmental factors determine the ensemble of glycans on any particular cell type, in a non-template encoded manner. As a consequence, the cell surface glycan profile provides a tightly-regulated temporal and spatial signature containing crucial biological information. This information is translated into biological functions by glycan binding proteins (GBPs), also called lectins. Importantly, our immune system is modulated by three major GBP families: C-type lectins, galectins, and Siglecs. The abilities of these GBPs to modulate immune cell function is intimately connected to their ability to differentiate ‘self’ or ‘non-self’ glycans from our own cells or pathogens, respectively. Hence, GBP–glycan interactions are critical mediators in immune cell homeostasis. Genetic manipulation of glycan processing enzymes has shed light on the roles of glycans in pathologies such as autoimmune diseases and cancer. However, genetic tools such as genomic manipulation and transgenic animal models have shown to be insufficient to fully untangle the roles of GBP-glycan interactions. Accordingly, recent advances in our understanding of GBPs and how they control immune cell function via glycan recognition has been driven by the development of chemical tools.

In this Research Topic, we explore recent work illuminating the various roles of glycans and/or GBPs in controlling immune cell function with special emphasis placed on chemical biology approaches that have been instrumental in such efforts. Potential subjects covered may include:

• Immunological roles of Glycan-binding proteins
• Glycans as immunomodulators
• Development of ligands to probe glycan-binding proteins
• Chemical biology approaches to modulate glycan-binding proteins and their glycan ligands
• Glycans and synthetic derivatives as novel adjuvants
• Glycan-based targeted delivery
• Intracellular glycosylation in immune cells
• Tissue homing of immune cells mediated by glycans
• Glycolipid presentation to immune cells
• Glycan-based vaccines
• Analytical methods for functional characterization of lectin-glycan interactions