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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Motifs
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Animals
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Blotting, Western
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Cell Movement
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Concanavalin A / pharmacology
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Electrophoresis, Polyacrylamide Gel
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Hepatitis, Animal / chemically induced
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Hepatitis, Animal / immunology*
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Immunohistochemistry
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Integrins / biosynthesis
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Integrins / immunology
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Killer Cells, Natural / immunology*
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Liver / immunology
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Liver / pathology
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Lymphocyte Activation / drug effects
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Lymphocyte Activation / immunology*
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Male
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Mice
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Models, Immunological
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Osteopontin
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Reverse Transcriptase Polymerase Chain Reaction
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Sialoglycoproteins / deficiency
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Sialoglycoproteins / immunology*
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Signal Transduction / immunology
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T-Lymphocyte Subsets / immunology*
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Thrombin / metabolism
Substances
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Integrins
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Sialoglycoproteins
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Spp1 protein, mouse
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Osteopontin
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Concanavalin A
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Thrombin