Involvement of T cell Ig Mucin-3 (Tim-3) in the negative regulation of inflammatory bowel disease

Clin Immunol. 2010 Feb;134(2):169-77. doi: 10.1016/j.clim.2009.09.012. Epub 2009 Nov 13.

Abstract

Augmented intestinal T cells, especially CD4(+)T cells, are involved in the pathogenesis of inflammatory bowel disease (IBD). We used a murine 2, 4, 6-trinitrobenzene sulfonic acid (TNBS)-induced colitis model to investigate whether Tim-3, a negative regulator of CD4(+)T cells, is involved in the suppression of IBD. We found that blocking the Tim-3 signal pathway exacerbated TNBS-induced colitis, as shown by increased weight loss and aggravated tissue injury. Blockade of the Tim-3 pathway resulted in an increase in Tim-3(+)CD4T cells, a biased T effector cell response, and a decrease in Treg cells. It also resulted in an altered profile of co-stimulatory molecules expressed on lymphocytes, which partially explained the biased polarization of different T cell subsets. Our data suggest that the Tim-3 pathway is highly involved in the negative regulation of IBD. A better understanding of this pathway may shed new light on the pathogenesis of this disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology
  • Cell Separation
  • Cytokines / analysis
  • Cytokines / immunology
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Hepatitis A Virus Cellular Receptor 2
  • Inflammatory Bowel Diseases / chemically induced
  • Inflammatory Bowel Diseases / immunology*
  • Inflammatory Bowel Diseases / pathology
  • Mice
  • Mice, Inbred BALB C
  • Receptors, Virus / immunology*
  • Signal Transduction / immunology*
  • T-Lymphocyte Subsets / immunology
  • Trinitrobenzenesulfonic Acid / toxicity

Substances

  • Cytokines
  • Havcr2 protein, mouse
  • Hepatitis A Virus Cellular Receptor 2
  • Receptors, Virus
  • Trinitrobenzenesulfonic Acid