Galectin-9

Galectin-9 is a tandem-repeat galectin composed of two carbohydrate-recognition domains connected by a flexible linker, binding β-galactoside glycans with high affinity. Identified originally as an eosinophil chemoattractant, galectin-9 has become recognized as a key regulatory lectin of the Tim-3 inhibitory checkpoint pathway: it binds Tim-3 on terminally exhausted T cells and suppresses autoimmune and antitumor Th1/Tc1 responses, with its ligand network extended to CD44, PDI, Dectin-1 and IgE. Galectin-9 is abundantly produced by regulatory T cells, tolerogenic dendritic cells, macrophages and endothelium, and induces apoptosis or dysfunction of effector T cells, NK cells and Th17 cells while expanding Tregs and M2 macrophages. These properties make galectin-9 central to tumor immune evasion, maternal-fetal tolerance, transplantation tolerance and resolution of autoinflammation; paradoxically, it also exhibits potent antimicrobial and antiviral (HIV, dengue) activities by crosslinking pathogen glycans and is elevated as a biomarker in dengue severity, chronic infection and asthma exacerbation.