Galectin-3 exacerbates autoimmune diabetes by limiting regulatory T cell differentiation and function
- Lingxiang Xie
- Rong Zhang
- Hailan Zou
- Jingyi Hu
- Jiangming Deng
- Jin Ding
- Long Liu
- Qiuqiu Lin
- Bin Zhao
- Aimin Xu
- Zhiguang Zhou
- Yang Xiao
2026-01-01
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. Here, we report that compared to healthy controls, patients with T1D and their first-degree relatives (FDRs) exhibited significantly increased serum Galectin-3 levels primarily produced and secreted by monocytes/macrophages. Pharmacological inhibition (TD139) as well as knockout of Galectin-3 gene both attenuated Galectin-3–mediated suppression of regulatory T cells (T reg cells) and protected from insulitis and diabetes onset in NOD mice. Mechanistically, Galectin-3 bound to and activated lymphocyte activation gene 3 (LAG3), a receptor expressed on activated T cells, subsequently suppressing the MEK/ERK signaling pathway and thereby hindering T reg cell differentiation and function. In summary, our study identifies Galectin-3 as a potential biomarker for T1D and suggests that TD139 holds promise as a therapeutic candidate for patients with T1D and high serum Galectin-3 levels.