Osteopontin as a Mediator of NKT Cell Function in T Cell-Mediated Liver Diseases
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 t...
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Veröffentlicht in: | Immunity (Cambridge, Mass.) Mass.), 2004-10, Vol.21 (4), p.539-550 |
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Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | 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. |
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ISSN: | 1074-7613 1097-4180 |
DOI: | 10.1016/j.immuni.2004.08.012 |