Elucidation of molecular mechanisms for the regulation of immune response by reconstruction of microenvironment and analyses of transcription factors and their networks

通过微环境重建和转录因子及其网络分析阐明免疫反应调节的分子机制

• 批准号: 21390077
• 负责人: SHIMIZU Akira
• 金额: $ 11.73万
• 依托单位: Kyoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009-04-01 至 2013-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21390077/
• 关键词: 分子免疫学; 免疫制御; 転写因子; 遺伝子組換え; 抗体遺伝子; 発現制御; 免疫学; 遺伝子; 腸管免疫; 制御性T細胞; IgA; Runx; retinoic acid; TGF-β1; 自己免疫炎症; クラススイッチ

It is essential for proper for proper progression of immune reaction that construction of specific microenvironment and harmonized function of a variety of immuno-competent cells. It is tried to elucidate molecular mechanisms of such immune reaction by reconstruction of such microenvironment in vitro and analyses of transcription factors and their networks regulated by such microenvironment.An in vitro culture system that very efficiently induces class switching to IgA was established. It was found that Runx transcription factors are essential for IgA class switching and they act downstream of signals from retinoic acid TGF-beta1, and that Runx3 is essential for differentiation and maturation of regulatory T cells.

免疫反应的正常进行需要特定微环境的构建和多种免疫活性细胞功能的协调。 本研究试图通过体外构建该微环境，分析其调控的转录因子及其网络，阐明该免疫反应的分子机制，并建立了一种能高效诱导伊加类转换的体外培养体系。 发现Runx转录因子对于伊加类别转换是必需的，并且它们在来自视黄酸TGF-β 1的信号下游起作用，并且Runx 3对于调节性T细胞的分化和成熟是必需的。

项目成果

Cross-priming of CD8+ T cells in vivo by dendritic cells pulsed with autologous apoptotic leukemic cells in immunotherapy for elderly patients with acute myeloid leukemia

• DOI: 10.1016/j.exphem.2011.01.001
• 发表时间: 2011-04-01
• 期刊: EXPERIMENTAL HEMATOLOGY
• 影响因子: 2.6
• 作者: Kitawaki, Toshio;Kadowaki, Norimitsu;Uchiyama, Takashi
• 通讯作者: Uchiyama, Takashi

Safety and pharmacokinetics of recombinant human hepatocyte growth factor (rh-HGF) in patients with fulminant hepatitis: a phase I/II clinical trial, following preclinical studies to ensure safety.

• DOI: 10.1186/1479-5876-9-55
• 发表时间: 2011-05-08
• 期刊: Journal of translational medicine
• 影响因子: 7.4
• 作者: Ido A;Moriuchi A;Numata M;Murayama T;Teramukai S;Marusawa H;Yamaji N;Setoyama H;Kim ID;Chiba T;Higuchi S;Yokode M;Fukushima M;Shimizu A;Tsubouchi H
• 通讯作者: Tsubouchi H

Graded Attenuation of TCR Signaling Elicits Distinct Autoimmune Diseases by Altering Thymic T Cell Selection and Regulatory T Cell Function

• DOI: 10.4049/jimmunol.1000848
• 发表时间: 2010-08-15
• 期刊: JOURNAL OF IMMUNOLOGY
• 影响因子: 4.4
• 作者: Tanaka, Satoshi;Maeda, Shinji;Sakaguchi, Shimon
• 通讯作者: Sakaguchi, Shimon

CXCL13 production by an established lymph node stromal cell line via lymphotoxin-beta receptor engagement involves the cooperation of multiple signaling pathways.

• DOI: 10.1093/intimm/dxp014
• 发表时间: 2009-04
• 期刊: International immunology
• 影响因子: 4.4
• 作者: H. Suto;T. Katakai;M. Sugai;T. Kinashi;A. Shimizu

Id2 controls chondrogenesis acting downstream of BMP signaling during maxillary morphogenesis

Id2 在上颌形态发生过程中控制软骨形成，作用于 BMP 信号下游

• 发表时间: 2012
• 期刊: Bone
• 影响因子: 4.1
• 作者: Sakata-Goto;T.;Takahashi;K.;Kiso;H.;Huang;B.;Tsukamoto;H.;Takemoto;M.;Hayashi;T.;Sugai;M.;Nakamura;T.;Yokota;Y.;Shimizu;A.;Slavkin;H.;Bessho;K.
• 通讯作者: K.