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.

类风湿性关节炎 (RA) 是世界上最严重的医学问题之一，世界上约有 1% 的人受到影响。该疾病本质上是自身免疫性疾病，其特征是多个关节滑膜组织的慢性炎症。尽管发病机制尚未完全阐明，但关节中的表达是该疾病的特征。我们一直在使用我们最初开发的两种关节炎模型（HTLV-I）来研究该疾病的发病机制。 Tg) 小鼠和 IL-1 受体拮抗剂缺陷 (IL-1Ra KO) 小鼠在本研究中，我们分析了 IL-17 家族细胞因子在自身免疫性疾病发展中的作用以及通过 DC 激活诱导 Th17 的机制。发现 1) IL-17A 而不是 IL-17F 在自身免疫性疾病和炎症性疾病的发展中发挥重要作用，2) IL-17A 和 IL-17F 在宿主防御中都发挥重要作用3) Dectin-1和Dectin-2分别是DC上β-葡聚糖和α-甘露聚糖的受体，通过激活DC诱导Th17分化，并在宿主防御细菌感染中发挥重要作用这些发现应该可用于开发针对自身免疫性疾病和真菌感染的新疗法。

项目成果

IL-17 is involved in Helicobacter pylori-induced gastric inflammatory responses in a mouse model.

• DOI: 10.1111/j.1523-5378.2008.00629.x
• 发表时间: 2008-12
• 期刊: Helicobacter
• 影响因子: 4.4
• 作者: Shiomi S;Toriie A;Imamura S;Konishi H;Mitsufuji S;Iwakura Y;Yamaoka Y;Ota H;Yamamoto T;Imanishi J;Kita M
• 通讯作者: Kita M

Involvement of IL-17A in the pathogenesis of DSS-induced colitis in mice

• DOI: 10.1016/j.bbrc.2008.09.019
• 发表时间: 2008-12-05
• 期刊: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
• 影响因子: 3.1
• 作者: Ito, Reiko;Kita, Masakazu;Mazda, Osam
• 通讯作者: Mazda, Osam

Tyrosine Kinase 2 Plays Critical Roles in the Pathogenic CD4 T Cell Responses for the Development of Experimental Autoimmune Encephalomyelitis

• DOI: 10.4049/jimmunol.0902740
• 发表时间: 2009-12-01
• 期刊: JOURNAL OF IMMUNOLOGY
• 影响因子: 4.4
• 作者: Oyamada, Akiko;Ikebe, Hiori;Yamada, Hisakata
• 通讯作者: Yamada, Hisakata

Endogenous IL-17 Does Not Play a Significant Role in the Development of Experimental Murine Allergic Conjunctivitis

• DOI: 10.1159/000142043
• 发表时间: 2008-01-01
• 期刊: INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY
• 影响因子: 2.8
• 作者: Fukushima, Atsuki;Sumi, Tamaki;Ueno, Hisayuki
• 通讯作者: Ueno, Hisayuki

Interleukin-17 Promotes Autoimmunity by Triggering a Positive-Feedback Loop via Interleukin-6 Induction

• DOI: 10.1016/j.immuni.2008.07.018
• 发表时间: 2008-10-17
• 期刊: IMMUNITY
• 影响因子: 32.4
• 作者: Ogura, Hideki;Murakami, Masaaki;Hirano, Toshio
• 通讯作者: Hirano, Toshio