Galectin-4

Galectin-4 is a β-galactoside-binding tandem-repeat lectin with two carbohydrate-recognition domains, mostly expressed in intestinal epithelial cells and secreted extracellularly^[1]. Mechanistically, its two domains bind different ligands simultaneously, enabling crosslinking roles in lipid raft stabilization, protein apical trafficking, cell adhesion, wound healing, intestinal inflammation, and tumor progression^[1]. In intestinal inflammation, galectin-4 binds activated peripheral and mucosal lamina propria T cells at the CD3 epitope, inhibits T cell activation, cycling, and expansion, and induces calpain-dependent apoptosis^[2]. In experimental colitis, galectin-4 ameliorates mucosal inflammation, induces mucosal T cell apoptosis, and decreases pro-inflammatory cytokines including IL-17^[2]. In cancer models, extracellular galectin-4 drives immune evasion in pancreatic ductal adenocarcinoma by inducing T cell apoptosis through CD3ε/δ N-glycosylation binding^[3]. Compared with related mouse isoforms, galectin-4 and galectin-6 show similar digestive-tract expression, but galectin-4 uniquely appears in the lamina propria of DSS-damaged colon and associates with luminal colonic bacteria^[4]. For experimental applications, galectin-4 administration enhances cancer vaccine, PD-1 blockade, and antiviral CD8+ T cell responses, while antisense blockade reduces TNF-α inhibitor-induced T cell death^[2][5].

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