Siglecs as potential targets of therapy in human mast cell- and/or eosinophil-associated diseases

Abstract

Siglecs (sialic acid-binding immunoglobulin-like lectins) are a family of vertebrate glycan-binding cell-surface proteins. The majority mediate cellular inhibitory activity once engaged by specific ligands or ligand-mimicking molecules. As a result, Siglec engagement is now of interest as a strategy to therapeutically dampen unwanted cellular responses. When considering allergic inflammation, human eosinophils and mast cells express overlapping but distinct patterns of Siglecs. For example, Siglec-6 is selectively and prominently expressed on mast cells while Siglec-8 is highly specific for both eosinophils and mast cells. This review will focus on a subset of Siglecs and their various endogenous or synthetic sialoside ligands that regulate eosinophil and mast cell function and survival. It will also summarize how certain Siglecs have become the focus of novel therapies for allergic and other eosinophil- and mast cell-related diseases.