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j.gastro.2013.03.011.pdf | 6.99 MB | Adobe PDF | 見る/開く |
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dc.contributor.author | Maruoka, Ryutaro | en |
dc.contributor.author | Aoki, Nobuhiro | en |
dc.contributor.author | Kido, Masahiro | en |
dc.contributor.author | Iwamoto, Satoru | en |
dc.contributor.author | Nishiura, Hisayo | en |
dc.contributor.author | Ikeda, Aki | en |
dc.contributor.author | Chiba, Tsutomu | en |
dc.contributor.author | Watanabe, Norihiko | en |
dc.contributor.alternative | 渡部, 則彦 | ja |
dc.date.accessioned | 2013-08-28T00:46:32Z | - |
dc.date.available | 2013-08-28T00:46:32Z | - |
dc.date.issued | 2013-07 | - |
dc.identifier.issn | 0016-5085 | - |
dc.identifier.uri | http://hdl.handle.net/2433/178171 | - |
dc.description.abstract | [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hepatitis (AIH) initially respond to treatment with corticosteroids but often experience a relapse after treatment is withdrawn.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. | en |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Elsevier Inc. | en |
dc.rights | © 2013 AGA Institute. Published by Elsevier Inc. | en |
dc.rights | This is not the published version. Please cite only the published version. | en |
dc.rights | 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。 | ja |
dc.subject | Autoimmunity | en |
dc.subject | ANA | en |
dc.subject | Necrosis | en |
dc.subject | T-Cell Response | en |
dc.title | Splenectomy prolongs the effects of corticosteroids in mouse models of autoimmune hepatitis. | en |
dc.type | journal article | - |
dc.type.niitype | Journal Article | - |
dc.identifier.ncid | AA0065394X | - |
dc.identifier.jtitle | Gastroenterology | en |
dc.identifier.volume | 145 | - |
dc.identifier.issue | 1 | - |
dc.identifier.spage | 209 | - |
dc.identifier.epage | 220.e9 | - |
dc.relation.doi | 10.1053/j.gastro.2013.03.011 | - |
dc.textversion | author | - |
dc.identifier.pmid | 23523671 | - |
dcterms.accessRights | open access | - |
出現コレクション: | 学術雑誌掲載論文等 |
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