Osteopontin as a mediator of NKT cell function in T cell-mediated liver diseases |
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Authors: | Diao Hongyan Kon Shigeyuki Iwabuchi Kazuya Kimura Chiemi Morimoto Junko Ito Daisuke Segawa Tatsuya Maeda Masahiro Hamuro Junji Nakayama Toshinori Taniguchi Masaru Yagita Hideo Van Kaer Luc Onóe Kazunori Denhardt David Rittling Susan Uede Toshimitsu |
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Institution: | Division of Molecular Immunology, Hokkaido University, Sapporo 060-0815, Japan. |
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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. |
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