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

Diao H, Kon S, Iwabuchi K, Kimura C, Morimoto J, Ito D, Segawa T, Maeda M, Hamuro J, Nakayama T, Taniguchi M, Yagita H, Van Kaer L, OnĂ³e K, Denhardt D, Rittling S, Uede T
Immunity. 2004 21 (4): 539-50

PMID: 15485631 · 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.

MeSH Terms (21)

Amino Acid Motifs Animals Blotting, Western Cell Movement Concanavalin A Electrophoresis, Polyacrylamide Gel Hepatitis, Animal Immunohistochemistry Integrins Killer Cells, Natural Liver Lymphocyte Activation Male Mice Models, Immunological Osteopontin Reverse Transcriptase Polymerase Chain Reaction Sialoglycoproteins Signal Transduction T-Lymphocyte Subsets Thrombin

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