Galectin

About: Galectin is a research topic. Over the lifetime, 2076 publications have been published within this topic receiving 103409 citations. The topic is also known as: IPR001079 & Galectin.

Lectins as Pattern Recognition Molecules: The Effects of Epitope Density in Innate Immunity#

Abstract: The innate immune response of multicellular organisms is initiated by the binding of soluble and membrane-bound host molecules including lectins to the surface of pathogenic organisms. Until recently, it was believed that the epitopes recognized by host molecules were uniquely associated with the pathogenic organisms. Hence, the term pattern recognition receptors (PRRs) was used to describe their binding specificities. However, with an expanding number of lectin classes including C-type lectins, siglecs, and galectins recognized as PRRs, it is apparent that many of the glycan epitopes recognized on foreign pathogens are present in the host and involved in cellular functions. Hence, the molecular basis for pattern recognition by lectins of carbohydrate epitopes on pathogens is in question. A number of studies indicate that the density and number of glycan epitopes in multivalent carbohydrates and glycoprotein receptors determine the affinity of lectins and their effector functions. This paper reviews lectins that are involved in innate immunity, mechanisms of enhanced affinity and cross-linking of lectins with density-dependent glycan epitopes, density-dependent recognition of glycan receptors by lectins in host systems and lectin-glycan interactions in foreign pathogens. Evidence indicates that lectin pattern recognition in innate immunity is part of a general mechanism of density-dependent glycan recognition. This leads to a new definition of lectin receptor in biological systems, which considers the density and number of glycan epitopes on the surface of cells and not just the affinity of single epitopes.

Galectin-3 drives glycosphingolipid-dependent biogenesis of clathrin-independent carriers

Abstract: Several cell surface molecules including signalling receptors are internalized by clathrin-independent endocytosis. How this process is initiated, how cargo proteins are sorted and membranes are bent remains unknown. Here, we found that a carbohydrate-binding protein, galectin-3 (Gal3), triggered the glycosphingolipid (GSL)-dependent biogenesis of a morphologically distinct class of endocytic structures, termed clathrin-independent carriers (CLICs). Super-resolution and reconstitution studies showed that Gal3 required GSLs for clustering and membrane bending. Gal3 interacted with a defined set of cargo proteins. Cellular uptake of the CLIC cargo CD44 was dependent on Gal3, GSLs and branched N-glycosylation. Endocytosis of β1-integrin was also reliant on Gal3. Analysis of different galectins revealed a distinct profile of cargoes and uptake structures, suggesting the existence of different CLIC populations. We conclude that Gal3 functionally integrates carbohydrate specificity on cargo proteins with the capacity of GSLs to drive clathrin-independent plasma membrane bending as a first step of CLIC biogenesis.

Tim-3/Galectin-9 Pathway: Regulation of Th1 Immunity through Promotion of CD11b+Ly-6G+ Myeloid Cells

Abstract: IFN-gamma plays a central role in antitumor immunity. T cell Ig and mucin domain (Tim-3) is expressed on IFN-gamma-producing Th1 cells; on interaction with its ligand, galectin-9, Th1 immunity is terminated. In this study, we show that transgenic overexpression of Tim-3 on T cells results in an increase in CD11b(+)Ly-6G(+) cells and inhibition of immune responses. Molecular characterization of CD11b(+)Ly-6G(+) cells reveals a phenotype consistent with granulocytic myeloid-derived suppressor cells. Accordingly, we find that modulation of the Tim-3/galectin-9 (Gal-9) pathway impacts on tumor growth. Similarly, overexpression of Tim-3 ligand, Gal-9, results in an increase in CD11b(+)Ly-6G(+) cells and inhibition of immune responses. Loss of Tim-3 restores normal levels of CD11b(+)Ly-6G(+) cells and normal immune responses in Gal-9 transgenic mice. Our data uncover a novel mechanism by which the Tim-3/Gal-9 pathway regulates immune responses and identifies this pathway as a therapeutic target in diseases where myeloid-derived suppressor cells are disadvantageous.

An Emerging Role for Galectins in Tuning the Immune Response: Lessons from Experimental Models of Inflammatory Disease, Autoimmunity and Cancer

Abstract: Inflammation is a critical process for eliminating pathogens, but can lead to serious deleterious effects if left unchecked Identifying the endogenous factors that control immune tolerance and inflammation is a key goal in the field of immunology Galectins, a family of endogenous lectins with affinity for beta-galactoside-containing oligosaccharides, are expressed by several cells of the immune system and tissue-resident stromal cells According to their architecture, this family of glycan-binding proteins is classified in those containing one-carbohydrate-recognition domain (CRD) (proto-type), those containing two-CRD joined by a linker non-lectin domain (tandem-repeat) and those that have one-CRD attached to an N-terminal peptide (chimera-type) Accumulating evidence indicates that galectins play critical regulatory roles in immune cell response and homeostasis In this review, we summarize recent developments in our understanding of the galectins' roles within different immune cell compartments, and in the broader context of the inflammatory microenvironments In particular we illustrate the immunoregulatory role of three representative members of each galectin subfamily: galectin-1, -3 and -9 This body of knowledge, documenting the coming of age of galectins as potential immunosuppressive agents or targets for anti-inflammatory drugs, represents a sound basis to further explore their potential as novel therapies for autoimmune diseases, chronic inflammation and cancer