Dysregulated upregulation of T-cell immunoglobulin and mucin domain-3 on mucosal T helper 1 cells in patients with Crohn's disease

Abstract

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.

Key Words::

• Crohn's disease
• galectin-9
• inflammatory bowel disease
• T-cell immunoglobulin and mucin domain 3 (TIM-3)

Acknowledgements

This work was supported in part by Health and Labour Sciences Research Grants for research on intractable diseases from Ministry of Health, Labour and Welfare of Japan.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.