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j.gastro.2013.03.011.pdf | 6.99 MB | Adobe PDF | 見る/開く |
タイトル: | Splenectomy prolongs the effects of corticosteroids in mouse models of autoimmune hepatitis. |
著者: | Maruoka, Ryutaro Aoki, Nobuhiro Kido, Masahiro Iwamoto, Satoru Nishiura, Hisayo Ikeda, Aki Chiba, Tsutomu ![]() Watanabe, Norihiko |
著者名の別形: | 渡部, 則彦 |
キーワード: | Autoimmunity ANA Necrosis T-Cell Response |
発行日: | Jul-2013 |
出版者: | Elsevier Inc. |
誌名: | Gastroenterology |
巻: | 145 |
号: | 1 |
開始ページ: | 209 |
終了ページ: | 220.e9 |
抄録: | [Background & Aims]Most patients with autoimmune hepatitis (AIH) initially respond to treatment with corticosteroids but often experience a relapse after treatment is withdrawn. BALB/c mice with disruption of programmed cell death 1 (PD-1^{–/–} mice) that undergo thymectomy 3 days after birth develop a deregulated immune system, have reduced numbers of Foxp3^+ regulatory T cells, and develop fulminant hepatic failure that resembles acute-onset AIH in humans. We examined whether splenectomy overcomes corticosteroid insufficiency and reduces the severity of AIH in these mice. We also developed a mouse model of chronic AIH to investigate the effects of splenectomy. [Methods]After thymectomy, BALB/c PD-1^{–/–} mice were treated with dexamethasone before or after induction of AIH; splenectomy was performed in mice that had and had not been treated with dexamethasone. Neonatal C57BL/6 PD-1^{–/–} mice underwent thymectomy to create a model of chronic AIH. [Results]Injection of dexamethasone before or after induction of AIH prevented development of fatal AIH in BALB/cPD-1^{–/–} mice. However, injection of dexamethasone after induction of AIH did not suppress splenic production of follicular helper T cells, and discontinuation of dexamethasone led to a relapse of AIH. Splenectomy (even without administration of dexamethasone) prevented AIH. Neonatal C57BL/6 PD-1^{–/–} mice that underwent thymectomy developed chronic hepatitis with fibrosis and hypergammaglobulinemia and produced antinuclear antibodies; AIH was found to be induced in the spleen. Splenectomy reduced liver inflammation in these mice and in BALB/c PD-1^{–/–} mice with AIH. [Conclusions]AIH can be induced in mice via disruption of PD-1 and thymectomy; these cause the same disruptions in immune regulation in BALB/c and C57BL/6 mice but produce different phenotypes. Splenectomy overcomes corticosteroid insufficiency in mice and prolongs the effects of dexamethasone. |
著作権等: | © 2013 AGA Institute. Published by Elsevier Inc. This is not the published version. Please cite only the published version. この論文は出版社版でありません。引用の際には出版社版をご確認ご利用ください。 |
URI: | http://hdl.handle.net/2433/178171 |
DOI(出版社版): | 10.1053/j.gastro.2013.03.011 |
PubMed ID: | 23523671 |
出現コレクション: | 学術雑誌掲載論文等 |
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