The transcriptomic landscape of Galectin-3-treated versus vehicle-treated Tregs

Galectin-3, a β-galactoside-binding lectin, has been implicated in several inflammatory and autoimmune diseases. However, the significance of circulating Galectin-3 in type 1 diabetes (T1D) remains unclear. Pharmacological inhibition (TD139) as well as knockout of the Galectin-3 gene both attenuated Galectin-3-mediated suppression of regulatory T cells (Tregs) and protected from insulitis and diabetes onset in NOD mice. To further elucidate the downstream mechanisms, we performed RNA-seq analysis to profile the transcriptomic landscape of Galectin-3-treated versus vehicle-treated Tregs. Mechanistically, Galectin-3 binds to and activates lymphocyte activation gene-3 (LAG3), a receptor expressed on activated T cells, subsequently suppressing the MEK/ERK signaling pathway and thereby hindering Treg differentiation and function.