Downregulating galectin-3 inhibits proinflammatory cytokine production by human monocyte-derived dendritic cells via RNA interference

• Galectin-3 (Gal-3), a β-galactoside-binding lectin, reprograms proinflammatory cytokine production in human MoDCs.
• Gal-3 siRNA upregulates IL-12 p35, IL-10, while downregulates IL-23 p19, IL-6, IL-1β in TLR/NLR-stimulated MoDCs.
• Gal-3 siRNA-treated human MoDCs inhibit Th2 and Th17 development.
• Intracellular Gal-3 acts as a cytokine hub of human DCs, independent of carbohydrate recognition domain (CRD).

Galectin-3 (Gal-3), a β-galactoside-binding lectin, serves as a pattern-recognition receptor (PRR) of dendritic cells (DCs) in regulating proinflammatory cytokine production. Galectin-3 (Gal-3) siRNA downregulates expression of IL-6, IL-1β and IL-23 p19, while upregulates IL-10 and IL-12 p35 in TLR/NLR stimulated human MoDCs. Furthermore, Gal-3 siRNA-treated MoDCs enhanced IFN-γ production in SEB-stimulated CD45RO CD4 T-cells, but attenuated IL-17A and IL-5 production by CD4 T-cells. Addition of neutralizing antibodies against Gal-3, or recombinant Gal-3 did not differentially modulate IL-23 p19 versus IL-12 p35. The data indicate that intracellular Gal-3 acts as cytokine hub of human DCs in responding to innate immunity signals. Gal-3 downregulation reprograms proinflammatory cytokine production by MoDCs that inhibit Th2/Th17 development.