TIM-1 and TIM-3 enhancement of Th2 cytokine production by mast cells

Blood. 2007 Oct 1;110(7):2565-8. doi: 10.1182/blood-2006-11-058800. Epub 2007 Jul 9.


Members of the T-cell immunoglobulin- and mucin-domain-containing molecule (TIM) family have roles in T-cell-mediated immune responses. TIM-1 and TIM-2 are predominantly expressed on T helper type 2 (Th2) cells, whereas TIM-3 is preferentially expressed on Th1 and Th17 cells. We found that TIM-1 and TIM-3, but neither TIM-2 nor TIM-4, were constitutively expressed on mouse peritoneal mast cells and bone marrow-derived cultured mast cells (BMCMCs). After IgE + Ag stimulation, TIM-1 expression was down-regulated on BMCMCs, whereas TIM-3 expression was up-regulated. We also found that recombinant mouse TIM-4 (rmTIM-4), which is a ligand for TIM-1, as well as an anti-TIM-3 polyclonal Ab, can promote interleukin-4 (IL-4), IL-6, and IL-13 production without enhancing degranulation in BMCMCs stimulated with IgE + Ag. Moreover, the anti-TIM-3 Ab, but neither anti-TIM-1 Ab nor rmTIM-4, suppressed mast-cell apoptosis. These observations suggest that TIM-1 and TIM-3 may be able to influence T-cell-mediated immune responses in part through effects on mast cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytokines / biosynthesis
  • Hepatitis A Virus Cellular Receptor 1
  • Hepatitis A Virus Cellular Receptor 2
  • Mast Cells / metabolism*
  • Membrane Proteins / classification
  • Membrane Proteins / metabolism*
  • Mice
  • Receptors, Virus / classification
  • Receptors, Virus / metabolism*
  • Th2 Cells / metabolism*


  • Cytokines
  • Havcr1 protein, mouse
  • Havcr2 protein, mouse
  • Hepatitis A Virus Cellular Receptor 1
  • Hepatitis A Virus Cellular Receptor 2
  • Membrane Proteins
  • Receptors, Virus
  • TIM-4 protein, mouse