Rebalancing the Immune System: Galectin-9 as a Potential Drug for inflammatory bowel diseases via TIM-3 Activation 3654

Abstract Description The T cell Immunoglobulin and Mucin domain (TIM) receptor family plays a pivotal role in immune regulation and has been implicated in the pathogenesis of autoimmune diseases. TIM-3, an inhibitory immune checkpoint receptor expressed on T cells and associated with the T cell receptor (TCR), induces apoptosis and regulates immune responses. Dysregulation of TIM-3 has been linked to autoimmune disorders and cancer. This study investigates the role of TIM-3 in inflammatory bowel diseases (IBD), such as ulcerative colitis (UC) and Crohn’s disease (CD), using blood and tissue samples from patients and healthy controls. Colonic biopsies and PBMCs were analyzed using single cell sequencing, qPCR, FACS, immunofluorescence, and cytokine analysis to evaluate TIM-3 expression and function. IBD patients exhibited elevated TIM-3 (HAVCR2) levels compared to controls. TCR-stimulated T cells showed increased HAVCR2 transcript and protein expression. Galectin-9, a TIM-3 ligand, was used to explore potential therapeutic effects. Activation of TIM-3 by galectin-9 induced apoptosis and decreased pro-inflammatory mediators as well as oxidative stress in PBMCs. Notably, galectin-9 expression was downregulated in IBD patients, suggesting its potential as a therapeutic agent. These findings highlight the TIM-3/galectin-9 axis as a promising molecular target for innovative IBD therapies. Topic Categories Immune Mechanisms of Human Disease (HUM)