TIM3 as a Crucial Regulator of Immune and Metabolic Homeostasis in IBD: Potential for Galectin 9 Therapy? 3655

Abstract Description Inflammatory bowel disease (IBD) is characterized by chronic gastrointestinal inflammation driven by dysregulated T cell activity and cytokine secretion. TIM3, a T cell immunoglobulin and mucin domain receptor with co-inhibitory effects on T cells, plays a key role not only in context with cancer but also IBD. However, the intracellular mechanisms by which TIM3 influences IBD remain poorly understood. To address this, we investigated TIM3 deficiency using an experimental colitis model. Through mini-endoscopy, histology, immunofluorescence staining, flow cytometry, ELISA, and untargeted metabolomic analysis of lamina propria mononuclear cells (LPMCs), we evaluated TIM3’s role in colitis and its metabolic implications. Additionally, we tested recombinant Galectin 9, a TIM3 ligand, as a potential therapeutic intervention. TIM3-deficient mice displayed aggravated colitis with increased T cell activity and an associated metabolic shift. Furthermore, a Galectin 9 administration in vitro induced T cell apoptosis, reducing T cell activity, in a dose-dependent manner. Importantly, Galectin 9 levels were reduced in chronic experimental colitis, underscoring its therapeutic potential. Our findings suggest that a TIM3 deficiency disrupts metabolic homeostasis and increases oxidative stress, highlighting TIM3’s dual role as a regulator of immune activation and metabolic balance. Galectin 9 emerges as a promising therapeutic target in IBD. Topic Categories Therapeutic Approaches to Autoimmunity (THER)