Molecular Mechanism of Regulation of the Cytokine Signal and Immunity

细胞因子信号与免疫调节的分子机制

• 批准号: 18109005
• 负责人: YOSHIMURA Akihiko
• 金额: $ 68.64万
• 依托单位: Keio University (2008-2009)Kyushu University (2006-2007)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (S)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18109005/
• 关键词: サイトカイン; シグナル伝達; チロシンキナーゼ; 転写因子; ヘルパーT; 細胞; 樹状細胞; Ras c-fos; ヘルパーT細胞; インターフェロン; SOCS; 炎症; アレルギー; 自己免疫疾患; STAT; 負の制御; 免疫制御; アレルギー自己免疫疾患; TGFβ; 抑制性T細胞

Cytokines play essential roles in regulation of innate and adaptive immunity. We have investigated the function of SOCS family and Spred/Sprouty family proteins which regulate cytokine signaling, by using genetically engineered mice. We found that SOCS1 and SOCS3 regulate helper T cell differentiation incuding Th17 and Tregs by modulating STAT transcription factors. We also found that human SPRED1 is responsible for neurofibromatosis type I like disease. Furthermore we discovered a novel mechanism of cAMP-mediated TLR signaling suppression through c-fos. We also found that Smad2/3 is essential for immunosuppression by TGF-beta.

细胞因子在调节先天免疫和适应性免疫中起重要作用。我们利用基因工程小鼠研究了SOCS家族和Spred/Sprouty家族蛋白调节细胞因子信号的功能。我们发现SOCS 1和SOCS 3通过调节STAT转录因子来调节辅助性T细胞的分化，包括Th 17和Tcl 2。我们还发现，人SPRED 1是负责神经纤维瘤病I型样疾病。此外，我们发现了一个新的机制，cAMP介导的TLR信号抑制通过c-fos。我们还发现Smad 2/3对于TGF-β的免疫抑制是必不可少的。

项目成果

Smad2 and Smad3 are redundantly essential for the TGF-beta-mediated regulation of regulatory T plasticity and Th1 development.

Smad2 和 Smad3 对于 TGF-β 介导的调节性 T 可塑性和 Th1 发育的调节至关重要。

• 发表时间: 2010
• 期刊: J Immunol.
• 作者: Takimoto T;Wakabayashi Y;Sekiya T;Takahashi R;et al.
• 通讯作者: et al.

Function of miR-146a in controlling Treg cell-mediated regulation of Th1 responses.

• DOI: 10.1016/j.cell.2010.08.012
• 发表时间: 2010-09-17
• 期刊: Cell
• 影响因子: 64.5
• 作者: Lu LF;Boldin MP;Chaudhry A;Lin LL;Taganov KD;Hanada T;Yoshimura A;Baltimore D;Rudensky AY
• 通讯作者: Rudensky AY

Role of SOCS1 in innate and adaptive immune tolerance World

SOCS1 在先天性和适应性免疫耐受中的作用 World

• 发表时间: 2010
• 作者: Y.Tamura;Y.Harada;K.Yamano;K.Watanabe;D.Ishikawa;C.Ohshima;S.Nishikawa;H.Yamamoto;T.Endo;Akihiko Yoshimura
• 通讯作者: Akihiko Yoshimura

Rajewsky K, Rudensky AY. Foxp3-dependent microRNA155 confers competitive fitness to regulatory T cells by targeting SOCS1 protein

Rajewsky K，鲁登斯基 AY。

• 发表时间: 2009
• 期刊: Immunity 30(1)
• 作者: Lu LF;Thai TH;Calado DP;Chaudhry A;Kubo M;Tanaka K;Loeb GB;Lee H;Yoshimura A
• 通讯作者: Yoshimura A

SOCS1 is a link between inflammation and inflammation-mediated carcinogenesis.

SOCS1 是炎症和炎症介导的癌发生之间的联系。

• 发表时间: 2007
• 作者: Hanada T;Tanaka K;Yoshimura A;et al.;Akihiko Yoshimura;Akihiko Yoshimura;Akihiko Yoshimura;Akihiko Yoshimura;Akihiko Yoshimura
• 通讯作者: Akihiko Yoshimura