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j.clim.2012.10.008.pdf | 11.26 MB | Adobe PDF | 見る/開く |
タイトル: | TNF-α is essential in the induction of fatal autoimmune hepatitis in mice through upregulation of hepatic CCL20 expression. |
著者: | Iwamoto, Satoru Kido, Masahiro Aoki, Nobuhiro Nishiura, Hisayo Maruoka, Ryutaro Ikeda, Aki Okazaki, Taku Chiba, Tsutomu ![]() Watanabe, Norihiko |
著者名の別形: | 渡部, 則彦 |
キーワード: | Mouse model Autoimmune hepatitis TNF-α CCL20 TNF-α antagonist |
発行日: | Jan-2013 |
出版者: | Elsevier Inc. |
誌名: | Clinical immunology |
巻: | 146 |
号: | 1 |
開始ページ: | 15 |
終了ページ: | 25 |
抄録: | It is unclear what roles TNF-α has in the development of autoimmune hepatitis (AIH) and whether AIH is responsive to anti-TNF-α. We recently developed a mouse model of fatal AIH that develops in PD-1-deficient mice thymectomized three days after birth, finding that CCR6-CCL20 axis-dependent migration of dysregulated splenic T cells is crucial to induce AIH. In this study, we show the indispensable role of TNF-α in the development of AIH. Administering anti-TNF-α prevented the induction, but treatment by anti-TNF-α after the induction did not suppress progression. Administering anti-TNF-α did not prevent splenic T-cell activation, but did suppress hepatic CCL20 expression. In contrast, administering anti-CCL20 suppressed AIH but not elevated serum TNF-α levels. TNF-α stimulation enhanced CCL20 expression in hepatocytes. These findings suggest that TNF-α is essential in the induction of AIH through upregulation of hepatic CCL20 expression, which allows migration of dysregulated splenic T cells. |
著作権等: | © 2012 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/2433/168391 |
DOI(出版社版): | 10.1016/j.clim.2012.10.008 |
PubMed ID: | 23178752 |
出現コレクション: | 学術雑誌掲載論文等 |
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