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タイトル: | IFN-γ is reciprocally involved in the concurrent development of organ-specific autoimmunity in the liver and stomach. |
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: | 岩本, 諭 |
キーワード: | IFN-γ proinflammatory mediator autoimmune gastritis CCL20 regulatory function autoimmune hepatitis |
発行日: | 13-Oct-2011 |
出版者: | Informa healthcare |
誌名: | Autoimmunity |
巻: | 45 |
号: | 2 |
開始ページ: | 186 |
終了ページ: | 198 |
抄録: | Interferon (IFN)-γ acts as a critical proinflammatory mediator in autoimmune processes, whereas it exerts regulatory functions to limit tissue damage associated with inflammation. However, a detailed understanding of the complex roles of IFN-γ in the development of organ-specific autoimmunity is still lacking. Recently, we found that programmed cell death 1-deficient mice thymectomized 3 days after birth (NTx-PD-1(- / - ) mice) concurrently developed autoimmune hepatitis (AIH) and autoimmune gastritis (AIG). In this study, we investigated the roles of IFN-γ in the development of AIH and AIG in this mouse model. In NTx-PD-1(- / - ) mice, serum levels of IFN-γ were markedly elevated. Neutralization of IFN-γ prevented the development of AIG. However, the same treatment exacerbated hepatic T-cell infiltration in AIH. Because of the loss of anti-proliferative effects by IFN-γ, neutralization of IFN-γ increased T-cell proliferation in the spleen and liver, resulting in exacerbated T-cell infiltration in the liver. On the other hand, in the development of AIG, CD4(+) T-cell migration into the gastric mucosa is essential for induction. CCL20 expression was up-regulated in the gastric mucosa, and anti-CCL20 suppressed CD4(+) T-cell infiltration into the gastric mucosa. Importantly, anti-IFN-γ suppressed CCL20 expression and infiltration of CD4(+) T cells in the gastric mucosa, whereas in vivo injection of recombinant IFN-γ up-regulated CCL20 expression in the stomach, suggesting that IFN-γ is critically involved in CD4(+) T-cell accumulation in AIG by up-regulating local CCL20 expression. In conclusion, IFN-γ is involved differently in the development of AIH and of AIG. IFN-γ negatively regulates T-cell proliferation in fatal AIH, whereas it initiates development of AIG. These findings imply that increased production of IFN-γ induced by an organ-specific autoimmunity may trigger the concurrent development of another organ-specific autoimmune disease. |
著作権等: | © 2012 Informa healthcare 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/2433/152418 |
DOI(出版社版): | 10.3109/08916934.2011.616559 |
PubMed ID: | 21995497 |
出現コレクション: | 学術雑誌掲載論文等 |
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