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Immunological aspects and therapeutic significance of an autoantibody against histone H1 in a rat model of concanavalin A‐induced hepatitis
Author(s) -
Nakano Toshiaki,
Goto Shigeru,
Lai ChiaYun,
Hsu LiWen,
Takaoka Yuki,
Kawamoto Seiji,
Chiang KueiChen,
Shimada Yayoi,
Ohmori Naoya,
Goto Takeshi,
Sato Shuji,
Ono Kazuhisa,
Cheng YuFan,
Chen ChaoLong
Publication year - 2010
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2009.03149.x
Subject(s) - autoantibody , histone h1 , concanavalin a , histone , immunology , biology , antibody , immune system , cancer research , biochemistry , in vitro , gene
Summary We previously demonstrated the immunosuppressive activity of anti‐histone H1 autoantibody induced in experimental and clinical liver allograft tolerance. This study aimed to explore the immunological aspects of anti‐histone H1 autoantibody in liver injury induced by concanavalin A (Con A). To establish a Con A‐hepatitis model, 20 mg/kg Con A was intravenously injected into rats, after which liver function and histopathological analyses were performed. In this model, anti‐histone H1 autoantibody was transiently induced in the sera during the natural recovery stage, 3–7 days after Con A injection. To evaluate the therapeutic significance of anti‐histone H1 autoantibody, a polyclonal antibody against histone H1 was intraperitoneally injected immediately after Con A injection. We found that injection of anti‐histone H1 antibody could reduce Con A‐induced liver damage. Further mechanical analyses revealed that anti‐histone H1 antibody altered the intracellular activation of mitogen‐activated protein kinase, nuclear factor‐κB and calcineurin via T‐cell receptor signalling, suggesting that anti‐histone H1 antibody may protect the liver from Con A‐induced injury by inhibiting activation of effector T cells. These findings suggest that anti‐histone H1 autoantibody may be a natural immune regulatory factor that protects inflamed livers suffering from autoimmune hepatitis and may lead to T‐cell unresponsiveness through the selective regulation of mitogen‐activated protein kinase/nuclear factor‐κB and calcineurin signalling.