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

Abstract

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.

• Authors: Hongyan Diao, Shigeyuki Kon, Kazuya Iwabuchi, Chiemi Kimura, Junko Morimoto, Daisuke Ito, Tatsuya Segawa, Masahiro Maeda, Junji Hamuro, Toshinori Nakayama, Masaru Taniguchi, Hideo Yagita, Luc Van Kaer, Kazunori Onóe, David Denhardt, Susan Rittling, Toshimitsu Uede
• Journal: Immunity (Immunity) Vol. 21 Issue 4 Pg. 539-50 (Oct 2004) ISSN: 1074-7613 [Print] United States
• PMID: 15485631 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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