IRF-4 is associated with the development of granulomas in autoimmune disease

IRF-4 与自身免疫性疾病肉芽肿的发生有关

• 批准号: 23591442
• 负责人: SEKINE Hideharu
• 金额: $ 3.24万
• 依托单位: Fukushima Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23591442/
• 关键词: IRF4; IRF1; 自己免疫; 肉芽腫; 国際情報交換; アメリカ; IRF-4; IRF-1

Mechanisms of granuloma formation in autoimmune diseases is unknown. We found that transcription factor IRF4-deficient lupus-prone MRL/lpr mice develop granulomas with Langhans giant cells in multiple organs including lung. We also found that IRF4-deficient MRL/lpr mice had increased numbers of IFN-g-producing Th1 cells with elevated levels of serum IFN-g. While, transcription factor IRF1-deficient MRL/lpr mice had increased numbers of IL-4-producing Th2 cells and granulomas with foreign body giant cells in their lung. Our data indicate that transcription factor IRF4 and IRF1 play important roles to maintain Th1/Th2-cell/cytokine balance, and defect of these transcription factors causes development of granulomatous lesions in multiple organs.

自身免疫性疾病中肉芽肿形成的机制尚不清楚。我们发现，转录因子IRF 4缺陷型狼疮易感MRL/lpr小鼠在包括肺在内的多个器官中发生肉芽肿，并伴有朗汉斯巨细胞。我们还发现IRF 4缺陷型MRL/lpr小鼠产生IFN-γ的Th 1细胞数量增加，血清IFN-γ水平升高。而转录因子IRF 1缺陷型MRL/lpr小鼠肺内产生IL-4的Th 2细胞和异物巨细胞肉芽肿数量增加。我们的数据表明，转录因子IRF 4和IRF 1发挥重要作用，以维持Th 1/Th 2-细胞/细胞因子的平衡，这些转录因子的缺陷导致肉芽肿性病变的发展，在多个器官。

项目成果

IRF-4 deficient lupus-prone MRL/lprmice develop granulomatous lesions in multiple organs with strong propensity for Th1 polarity

IRF-4缺陷型狼疮易感MRL/lp小鼠在多个器官中出现肉芽肿性病变，具有强烈的Th1极性倾向

• 发表时间: 2011
• 作者: Machida T;Honma K;Matsuyama T;YuiK;Ruiz P;Fujita T;Gilkeson GS;Sekine H
• 通讯作者: Sekine H

Comment on “Mannan-Binding Lectin-Associated Serine Protease (MASP)-1 Is Crucial for Lectin Pathway Activation in Human Serum, whereas neither MASP-1 nor MASP-3 Is Required for Alternative Pathway Function”

对“甘露聚糖结合凝集素相关丝氨酸蛋白酶 (MASP)-1 对于人血清中凝集素途径激活至关重要，而替代途径功能不需要 MASP-1 和 MASP-3”的评论

• DOI: 10.4049/jimmunol.1390002
• 发表时间: 2013
• 期刊: The Journal of Immunology
• 作者: Minoru Takahashi;H. Sekine;Y. Endo;T. Fujita
• 通讯作者: T. Fujita

IFN-γ-receptor-1 is expressed abundantly on splenic B cells of MRL/lpr mice and is involved in peripheral B-cell survival/maintenance and autoantibody production.

IFN-γ-受体-1 在 MRL/lpr 小鼠的脾 B 细胞上大量表达，并参与外周 B 细胞的存活/维持和自身抗体的产生。

• 发表时间: 2013
• 作者: Takeshi Machida;Natsumi Sakamoto;Kiri Honma;Toshifumi Matsuyama;Katsuyuki Yui;and Hideharu Sekine
• 通讯作者: and Hideharu Sekine

補体の検査法と意義,In臨床検査増刊号・ここまでわかった自己免疫疾患

补体检测方法及意义，临床检测特刊，迄今为止已知的自身免疫性疾病

• 发表时间: 2011
• 作者: Kawano S;Lin Q;Amano H;Kaneko T;Nishikawa K;Tsurui H;Tada N;Nishimura H,Takai T;Shirai T;Takasaki Y and Hirose S;関根英治(宮坂信之)
• 通讯作者: 関根英治(宮坂信之)

補体の異常値と疾患

补体水平异常与疾病

• 发表时间: 2013
• 期刊: 福島医学雑誌
• 作者: Uemura M;Fujimura Y;Ko S;et al.;関根英治,町田豪,坂本夏美,高橋実
• 通讯作者: 関根英治,町田豪,坂本夏美,高橋実