Promotion of tissue inflammation by the immune receptor Tim-3 expressed on innate immune cells

Science. 2007 Nov 16;318(5853):1141-3. doi: 10.1126/science.1148536.

Abstract

CD4+ T helper 1 (TH1) cells are important mediators of inflammation and are regulated by numerous pathways, including the negative immune receptor Tim-3. We found that Tim-3 is constitutively expressed on cells of the innate immune system in both mice and humans, and that it can synergize with Toll-like receptors. Moreover, an antibody agonist of Tim-3 acted as an adjuvant during induced immune responses, and Tim-3 ligation induced distinct signaling events in T cells and dendritic cells; the latter finding could explain the apparent divergent functions of Tim-3 in these cell types. Thus, by virtue of differential expression on innate versus adaptive immune cells, Tim-3 can either promote or terminate TH1 immunity and may be able to influence a range of inflammatory conditions.

Publication types

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

MeSH terms

  • Animals
  • Astrocytes / immunology
  • CD11b Antigen / immunology
  • Central Nervous System Neoplasms / immunology
  • Dendritic Cells / immunology
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Galectins / immunology
  • Glioblastoma / immunology
  • Hepatitis A Virus Cellular Receptor 2
  • Humans
  • Immunity, Innate
  • Inflammation Mediators / immunology*
  • Lipopolysaccharides / immunology
  • Macrophages / immunology
  • Membrane Proteins / biosynthesis
  • Membrane Proteins / immunology*
  • Mice
  • Microglia / immunology
  • Multiple Sclerosis / immunology
  • Rats
  • Receptors, Immunologic / biosynthesis
  • Receptors, Immunologic / immunology*
  • Receptors, Virus / biosynthesis
  • Receptors, Virus / immunology*
  • Signal Transduction
  • T-Lymphocytes / immunology
  • Th1 Cells / immunology*
  • Toll-Like Receptors

Substances

  • CD11b Antigen
  • Galectins
  • HAVCR2 protein, human
  • Havcr2 protein, mouse
  • Hepatitis A Virus Cellular Receptor 2
  • ITGAM protein, human
  • Inflammation Mediators
  • LGALS9 protein, human
  • Lipopolysaccharides
  • Membrane Proteins
  • Receptors, Immunologic
  • Receptors, Virus
  • Toll-Like Receptors