The roles of cytokines in the development of autoimmune deseases

细胞因子在自身免疫性疾病发展中的作用

• 批准号: 19059006
• 负责人: IWAKURA Yoichiro
• 金额: $ 32.26万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research on Priority Areas
• 财政年份: 2007
• 资助国家: 日本
• 起止时间: 2007 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-19059006/
• 关键词: IL-1; IL-17; 疾患モデル動物; ノックアウトマウス; C型レクチン; 自己免疫疾患; 慢性関節リウマチ; 疾患モデルマウス; 炎症性疾患; サイトカイン; Th17; IL-17A; 関節リウマチ; IL-17F; 自己応答性; 獲得免疫

Rheumatoid arthritis (RA) is one of the most serious medical problems worldwide with approximately 1% of the people in the world affected. The disease is autoimmune in nature and characterized by chronic inflammation of the synovial tissues in multiple joints. High levels of inflammatory cytokine expression in the joints are characteristics of the disease, although the pathogenesis has not been elucidated completely. We have been studying the pathogenesis of the disease using two arthritis models that we originally developed ; HTLV-I transgenic (HTLV-I Tg) mice and IL-1 receptor antagonist-deficient (IL-1Ra KO) mice. In this study, we analyzed the roles of IL-17 family cytokines in the development of autoimmune diseases and the mechanisms of Th17 induction through DC activation. We found that 1) IL-17A, but not IL-17F, plays an important role in the development of autoimmune diseases and inflammatory diseases, 2) Both IL-17A and IL-17F play important roles in the host defense against bacterial infections, 3) Both Dectin-1 and Dectin-2, which is a receptor for β-glucans and α-mannans, respectively, on DCs, induce Th17 differentiation through activation of DCs, and play important role in the host defense against fungal infections. These findings should be of use for the development of new therapeutics against autoimmune diseases and fungal infection.

风湿性关节炎（RA）是世界上最严重的医学问题之一，约占世界人口的1%。这种疾病本质上是自身免疫性的，其特征是多个关节中滑膜组织的慢性炎症。关节中高水平的炎性细胞因子表达是该疾病的特征，尽管发病机制尚未完全阐明。我们一直在使用我们最初开发的两种关节炎模型研究该疾病的发病机制; HTLV-I转基因（HTLV-I Tg）小鼠和IL-1受体拮抗剂缺陷（IL-1 Ra KO）小鼠。在这项研究中，我们分析了IL-17家族细胞因子在自身免疫性疾病的发展中的作用，以及通过DC活化诱导Th 17的机制。我们发现1）IL-17 A而不是IL-17 F在自身免疫性疾病和炎症性疾病的发展中起重要作用，2）IL-17 A和IL-17 F在宿主防御细菌感染中起重要作用，3）DCs上的Dectin-1和Dectin-2分别是β-葡聚糖和α-甘露聚糖的受体，通过激活DC诱导Th 17分化，在宿主抗真菌感染中发挥重要作用。这些发现将有助于开发抗自身免疫性疾病和真菌感染的新疗法。

项目成果

A protective function for interleukin 17A in T cell-mediated intestinal inflammation.

• DOI: 10.1038/ni.1736
• 发表时间: 2009-06
• 期刊: Nature immunology
• 影响因子: 30.5

A C-type lectin that involved in the host defense against fungi plays an important role in the development of autoimmune arthritis

参与宿主防御真菌的 C 型凝集素在自身免疫性关节炎的发展中发挥重要作用

• 发表时间: 2008
• 作者: inushi M;Sato M;Kanamoto A;Itoh A;Nagai S;Koyasu S;Dranoff G;and Tahara H;服部浩一;Shinobu Saijo
• 通讯作者: Shinobu Saijo

IFN-γ protects cerulein-induced acute pancreatitis by repressing NF-κB activation

• DOI: 10.4049/jimmunol.178.11.7385
• 发表时间: 2007-06-01
• 期刊: JOURNAL OF IMMUNOLOGY
• 影响因子: 4.4
• 作者: Hayashi, Takahito;Ishida, Yuko;Kondo, Toshikazu
• 通讯作者: Kondo, Toshikazu

Deoxynucleic acids from Cryptococcus neoformans activate myeloid dendritic cells via a TLR9-dependent pathway

• DOI: 10.4049/jimmunol.180.6.4067
• 发表时间: 2008-03-15
• 期刊: JOURNAL OF IMMUNOLOGY
• 影响因子: 4.4
• 作者: Nakamura, Kiwamu;Miyazato, Akiko;Kawakami, Kazuyoshi
• 通讯作者: Kawakami, Kazuyoshi

IL-23 enhances host Defense against vaccinia virus infection via a mechanism partly involving IL-17

• DOI: 10.4049/jimmunol.179.6.3917
• 发表时间: 2007-09-15
• 期刊: JOURNAL OF IMMUNOLOGY
• 影响因子: 4.4
• 作者: Kohyama, Shunsuke;Ohno, Satoshi;Matsui, Masanori
• 通讯作者: Matsui, Masanori