Glycobiology simplified: diverse roles of glycan recognition in inflammation

Abstract

Glycans and complementary glycan-binding proteins are essential components in the language of cell-cell interactions in immunity. The study of glycan function is the purview of glycobiology, which has often been presented as an unusually complex discipline. In fact, the human glycome, composed of all of its glycans, is built primarily from only 9 building blocks that are combined by enzymes (writers) with specific and limited biosynthetic capabilities into a tractable and increasingly accessible number of potential glycan patterns that are functionally read by several dozen human glycan-binding proteins (readers). Nowhere is the importance of glycan recognition better understood than in infection and immunity, and knowledge in this area has already led to glycan mimetic anti-infective and anti-inflammatory drugs. This review includes a brief tutorial on human glycobiology and a limited number of specific examples of glycan-binding protein-glycan interactions that initiate and regulate inflammation. Examples include representatives from different glycan-binding protein families, including the C-type lectins (E-selectin, P-selectin, dectin-1, and dectin-2), sialic acid-binding immunoglobulin-like lectins (sialic acid-binding immunoglobulin-like lectins 8 and 9), galectins (galectin-1, galectin-3, and galectin-9), as well as hyaluronic acid-binding proteins. As glycoscience technologies advance, opportunities for enhanced understanding of glycans and their roles in leukocyte cell biology provide increasing opportunities for discovery and therapeutic intervention.

Role of low-grade inflammation in osteoarthritis

“…Galectins are glycan binding-proteins that modulate cell–cell and cell–matrix interactions, and play important roles in inflammation [34]. Differential expression of galectin-1 in osteoarthritic cartilage was previously noted [35].…”

Studies on the Detection, Expression, Glycosylation, Dimerization, and Ligand Binding Properties of Mouse Siglec-E

“…Sialic acid-binding immunoglobulin-like lectins (Siglecs) 5 are cell surface receptors of the I-type lectin family (1) that are expressed on innate immune cells and bind to sialylated and non-sialylated ligands (2)(3)(4). There are two types of Siglecs, inhibitory and activating, named for their effect on innate immune cells upon ligand binding.…”

Galectin‐9: Diverse roles in hepatic immune homeostasis and inflammation

“…Glycobiology is the study of the structure and function of glycans (i.e., carbohydrates, saccharides, or simple sugars). Because they are dominantly expressed on all eukaryotic and prokaryotic cell surfaces, glycans play central roles in cell–cell and cell–pathogen interactions . Glycan‐binding proteins are involved at all stages of immunity and inflammation, from initiation through resolution.…”

“…Glycan‐binding proteins are involved at all stages of immunity and inflammation, from initiation through resolution. In humans, more than 80 glycan‐binding proteins have been described that fall into about a dozen structural families, each of which has a conserved carbohydrate recognition domain (CRD) . Galectins are a fascinating family of guanosine diphosphates that are secreted into the extracellular environment directly from the cytoplasm independently of the classical endoplasmic reticulum/Golgi trafficking machinery .…”