Expression of human TIM-1 and TIM-3 on lymphocytes from systemic lupus erythematosus patients

Scand J Immunol. 2008 Jan;67(1):63-70. doi: 10.1111/j.1365-3083.2007.02038.x.

Abstract

The T-cell immunoglobulin- and mucin-domain-containing molecules (TIMs) comprise a new family of cell surface molecules expressed on T cells. TIM-3 is expressed on T helper type 1 (Th1) cells and implicated in the pathogenesis of Th1-driven auto- and allo-immune diseases. TIM-1 is suggested to act as a co-stimulatory molecule for all T cells, but with potentially stronger effects on Th2 than Th1 cells and is associated with Th2-related immune diseases. However, the TIM molecules have not been investigated in the systemic lupus erythematosus (SLE). In this study, we examined the expression of TIM-1 and TIM-3 on peripheral blood mononuclear cells from SLE patients using quantitative real-time RT-PCR. An increased TIM-1 expression was detected in SLE patients, which correlates with interleukin-10 expression. We also found that there was a significant increase in the expression of TIM-1 in SLE patients with quite active disease (SLE disease activity index > 6), indicating that TIM-1 expression might be related to active clinical phases. In contrast, TIM-3 expression remained normal in SLE patients with low statistical power (34.89%). However, the expression of TIM-3 ligand, galectin-9 increased in SLE patients indicating an enhanced engagement of TIM-3 with its ligand in SLE, which may result in a decreased regulatory T-cell function as shown by the decreased expression of FoxP3 and TGF-beta1 in SLE. These data suggest that TIM-1 and TIM-3/TIM-3L are involved in the pathogenesis of SLE.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cells, Cultured
  • Cytokines / biosynthesis
  • Cytokines / genetics
  • Female
  • Hepatitis A Virus Cellular Receptor 1
  • Hepatitis A Virus Cellular Receptor 2
  • Humans
  • Lupus Erythematosus, Systemic / metabolism*
  • Lupus Erythematosus, Systemic / pathology
  • Lymphocytes / metabolism*
  • Male
  • Membrane Glycoproteins / biosynthesis
  • Membrane Glycoproteins / genetics*
  • Membrane Proteins / biosynthesis
  • Membrane Proteins / genetics*
  • Middle Aged
  • Receptors, Virus / biosynthesis
  • Receptors, Virus / genetics*

Substances

  • Cytokines
  • HAVCR1 protein, human
  • HAVCR2 protein, human
  • Hepatitis A Virus Cellular Receptor 1
  • Hepatitis A Virus Cellular Receptor 2
  • Membrane Glycoproteins
  • Membrane Proteins
  • Receptors, Virus