Intracellular Galectin-9 Enhances Proximal TCR Signaling and Potentiates Autoimmune Diseases

• Published in: The Journal of immunology (1950) Vol. 204; no. 5; pp. 1158 - 1172
• Main Authors: Chen, Heng-Yi, Wu, Yen-Fei, Chou, Feng-Cheng, Wu, Yu-Hsuan, Yeh, Li-Tzu, Lin, Kuo-I, Liu, Fu-Tong, Sytwu, Huey-Kang
• Format: Journal Article
• Language: English
• Published: United States 01-03-2020
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1901114

Galectin-9 is a risk gene in inflammatory bowel disease. By transcriptomic analyses of ileal biopsies and PBMCs from inflammatory bowel disease patients, we identified a positive correlation between galectin-9 expression and colitis severity. We observed that galectin-9-deficient T cells were less able to induce T cell-mediated colitis. However, several mouse-based studies reported that galectin-9 treatment induces T cell apoptosis and ameliorates autoimmune diseases in an exogenously modulated manner, indicating a complicated regulation of galectin-9 in T cells. We found that galectin-9 is expressed mainly inside T cells, and its secreted form is barely detected under physiological conditions. Endogenous galectin-9 was recruited to immune synapses upon T cell activation. Moreover, proximal TCR signaling was impaired in galectin-9-deficient T cells, and proliferation of these cells was decreased through an intracellularly modulated manner. Th17 cell differentiation was downregulated in galectin-9-deficient T cells, and this impairment can be rescued by strong TCR signaling. Taken together, these findings suggest that intracellular galectin-9 is a positive regulator of T cell activation and modulates the pathogenesis of autoimmune diseases.