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 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.
Division of Molecular Immunology, Hokkaido University, Sapporo 060-0815, Japan.
Hongyan
H
Diao
Shigeyuki
S
Kon
Kazuya
K
Iwabuchi
Chiemi
C
Kimura
Junko
J
Morimoto
Daisuke
D
Ito
Tatsuya
T
Segawa
Masahiro
M
Maeda
Junji
J
Hamuro
Toshinori
T
Nakayama
Masaru
M
Taniguchi
Hideo
H
Yagita
Luc
L
Van Kaer
Kazunori
K
Onóe
David
D
Denhardt
Susan
S
Rittling
Toshimitsu
T
Uede
D020816:Amino Acid Motifs; D000818:Animals; D015153:Blotting, Western; D002465:Cell Movement; D003208:Concanavalin A / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D006520:Hepatitis, Animal / Q000139:chemically induced / Q000276:immunology*; D007150:Immunohistochemistry; D016023:Integrins / Q000096:biosynthesis / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008099:Liver / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D008297:Male; D051379:Mice; D018448:Models, Immunological; D053495:Osteopontin; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012795:Sialoglycoproteins / Q000172:deficiency / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013917:Thrombin / Q000378:metabolism
D016023:Integrins; D012795:Sialoglycoproteins; C506896:Spp1 protein, mouse; D053495:Osteopontin; D003208:Concanavalin A; D013917:Thrombin