Objective: T-cell immunoglobulin and mucin domain-3 (TIM-3) is a unique cell surface molecule expressed on T helper 1 (Th1) cells. Engagement of TIM-3 by ligand galectin-9 leads to dampened Th1 immunity. We investigated TIM-3 and galectin-9 expression in inflammatory bowel disease (IBD) patients and in healthy controls, and evaluated the immune role of the TIM-3 pathway in Crohn's disease (CD) pathogenesis.
Material and methods: We used flow cytometry to investigate TIM-3 expression on mononuclear cells isolated from the intestinal mucosa and peripheral blood cells of patients with IBD and healthy controls. We also evaluated galectin-9 mRNA expression on endoscopically obtained intestinal mucosal cells.
Results: TIM-3 was constitutively expressed on Th cells isolated from the intestinal mucosa of IBD patients and healthy controls. While we observed low TIM-3 expression on Th cells isolated from peripheral blood mononuclear cells (PBMCs), high TIM-3 expression was induced by Th1 stimulation. The level of TIM-3 expression on Th cells isolated from intestinal mucosa and stimulated PBMCs was significantly lower in CD patients than in healthy controls.
Conclusions: Our data show that TIM-3 upregulation on Th1 cells is dysregulated in patients with CD. Low TIM-3 expression on Th1 cells may provide a clue toward resolution of the inflammation associated with chronic inflammatory disease. These findings should contribute to develop understanding of CD pathogenesis.