Galectin-3 exacerbates autoimmune diabetes by limiting regulatory T cell differentiation and function

Area of Science:

• Immunology
• Endocrinology
• Molecular Biology

Background:

• Galectin-3 is linked to inflammatory and autoimmune conditions.
• The role of circulating Galectin-3 in type 1 diabetes (T1D) is not well understood.

Purpose of the Study:

• To investigate the significance of serum Galectin-3 in T1D.
• To explore Galectin-3 as a potential therapeutic target for T1D.

Main Methods:

• Measured serum Galectin-3 levels in T1D patients and their first-degree relatives (FDRs).
• Utilized pharmacological inhibition (TD139) and gene knockout of Galectin-3 in NOD mice models.
• Investigated the interaction between Galectin-3, lymphocyte activation gene 3 (LAG3), and the MEK/ERK signaling pathway.

Main Results:

• T1D patients and FDRs showed significantly higher serum Galectin-3 levels compared to healthy controls.
• Galectin-3 was primarily produced and secreted by monocytes/macrophages.
• Inhibition or knockout of Galectin-3 attenuated suppression of regulatory T cells (Treg cells), protected against insulitis, and prevented diabetes onset in NOD mice.
• Galectin-3 activated LAG3 on T cells, suppressing the MEK/ERK pathway and impairing Treg cell differentiation and function.

Conclusions:

• Galectin-3 is a potential serum biomarker for T1D.
• TD139, a Galectin-3 inhibitor, demonstrates therapeutic promise for T1D, particularly in individuals with elevated Galectin-3 levels.