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.