Osteopontin as a mediator of NKT cell function in T cell-mediated liver diseases

Immunity. 2004 Oct;21(4):539-50. doi: 10.1016/j.immuni.2004.08.012.


Both osteopontin (OPN) and natural killer T (NKT) cells play a role in the development of immunological disorders. We examined a functional link between OPN and NKT cells. Concanavalin A (Con A)-induced hepatitis is a well-characterized murine model of T cell-mediated liver diseases. Here, we show that NKT cells secrete OPN, which augments NKT cell activation and triggers neutrophil infiltration and activation. Thus, OPN- and NKT cell-deficient mice were refractory to Con A-induced hepatitis. In addition, a neutralizing antibody specific for a cryptic epitope of OPN, exposed by thrombin cleavage, ameliorated hepatitis. These findings identify NKT cell-derived OPN as a novel target for the treatment of inflammatory liver diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Animals
  • Blotting, Western
  • Cell Movement
  • Concanavalin A / pharmacology
  • Electrophoresis, Polyacrylamide Gel
  • Hepatitis, Animal / chemically induced
  • Hepatitis, Animal / immunology*
  • Immunohistochemistry
  • Integrins / biosynthesis
  • Integrins / immunology
  • Killer Cells, Natural / immunology*
  • Liver / immunology
  • Liver / pathology
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology*
  • Male
  • Mice
  • Models, Immunological
  • Osteopontin
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sialoglycoproteins / deficiency
  • Sialoglycoproteins / immunology*
  • Signal Transduction / immunology
  • T-Lymphocyte Subsets / immunology*
  • Thrombin / metabolism


  • Integrins
  • Sialoglycoproteins
  • Spp1 protein, mouse
  • Osteopontin
  • Concanavalin A
  • Thrombin