The development of an innovative therapy for autoimmune diseases by controlling transcription factors in the regulatory T cells.

通过控制调节性 T 细胞中的转录因子开发一种治疗自身免疫性疾病的创新疗法。

• 批准号: 15591050
• 负责人: YOSHIKATA Misaki
• 金额: $ 2.24万
• 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 (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15591050/
• 关键词: regulatory T cells; transcription factors; autoimmune diseases; FOXP3; SOCS3; 転写因子; 分化誘導; cDNAクローニング; レトロウイルスベクター; トランスジェニックマウス; ホメオスタシス

Cb4(+)CD25(+)regulatory T cells (Treg) contributes in homeostasis of the immune system by controlling an immune response. Recent accumulated findings suggest naturally occurring CD4(+)CD25(+)regulatory T cells which develop at least in the thymus via autoreactivity positive selection consists of an distinct T cell subset. As it is known that transcription factors contribute in the determination of cell lineage and transduction of the transcription factors induces cell differentiation. In order to find Treg-specific transcription factors, we generated Treg-specific expression cDNA library by subtraction. Among the library, we found two factors ; the one is (189), and the other is FOXP3. Foxp3 is demonstrated to play a pivotal role in Treg development. Therefore, we subsequently extended our research to screen FOXP3-assocaited molecules. By two yeast hybrid, we found SOCS3 is associated with FOXP3. The association involves SH2 region of SOCS3 and 81-210 amino acids region of FOXP3. Furthermore, We found that FOXP3 is associated the endogenous SOCS3 in FOXP3-transfected Treg cell clone. Considering the role of SOCS3 in the signal transduction, it is of interest to imagine that SOCS3 contribute in the immune regulation via Treg development.

Cb 4（+）CD 25（+）调节性T细胞（Treg）通过控制免疫反应有助于免疫系统的稳态。最近积累的研究结果表明，天然存在的CD 4（+）CD 25（+）调节性T细胞至少在胸腺中通过自身反应性阳性选择发育，由不同的T细胞亚群组成。众所周知，转录因子参与细胞谱系的决定，并且转录因子的转导诱导细胞分化。为了寻找Treg特异性转录因子，我们采用差减法构建了Treg特异性表达cDNA文库。在文库中，我们发现了两个因子;一个是（189），另一个是FOXP 3。Foxp 3被证明在Treg发育中起关键作用。因此，我们随后将我们的研究扩展到筛选FOXP 3相关分子。通过酵母双杂交，我们发现SOCS 3与FOXP 3相关。SOCS 3的SH 2区与FOXP 3的81-210个氨基酸的区域相关。此外，我们发现FOXP 3在转染的Treg细胞克隆中与内源性SOCS 3相关。考虑到SOCS 3在信号转导中的作用，设想SOCS 3通过Treg发育在免疫调节中起作用是有意义的。

项目成果

Reconstitution of CD8+ T cells by retroviral transfer of the TCR alphabeta-chain genes isolated from a clonally expanded P815-infiltrating lymphocyte.

通过逆转录病毒转移从克隆扩增的 P815 浸润淋巴细胞中分离的 TCR 字母链基因来重建 CD8 T 细胞。

• 发表时间: 2003
• 期刊: J Immunol. 171(4)
• 作者: Tahara H;Fujio K;Araki Y;Setoguchi K;Misaki Y;Kitamura T;Yamamoto K.
• 通讯作者: Yamamoto K.

Evaluation of functional disability using the health assessment questionnaire Japanese Patients with Systemic Sclerosis

使用日本系统性硬化症患者健康评估问卷评估功能障碍

• 发表时间: 2003
• 期刊: J.Rheumatology 30
• 作者: Kuwana M;Sato S;Misaki Y et al.
• 通讯作者: Misaki Y et al.

Kobari Y, Misaki Y, Setoguchi K, et al.: "T cell accumulating in the inflamed joints of a spontaneous murine model of rheumatoid arthritis become restricted to common clonotype."International Immunology. 16(1). 131-138 (2004)

Kobari Y、Misaki Y、Setoguchi K 等人：“类风湿性关节炎自发鼠模型发炎关节中积累的 T 细胞被限制为常见克隆型。”国际免疫学。

Tabara H, Fujo K, Misaki Y, et al.: "Reconstituted of CD8 T Cells by retroviral transfer of the TCR alphabeta-chain genes isolated from a clonally expanded."Journal of Immunology. 171(4). 2154-2160 (2003)

Tabara H、Fujo K、Misaki Y 等人：“通过逆转录病毒转移从克隆扩增中分离的 TCR 字母链基因来重建 CD8 T 细胞。”免疫学杂志。

T cells accumulating in the inflamed joints of a spontaneous murine model of rheumatoid arthritis become restricted to common clonotypes during disease progression

在类风湿性关节炎自发小鼠模型的发炎关节中积累的 T 细胞在疾病进展过程中变得仅限于常见克隆型

• 发表时间: 2004
• 期刊: Int.Immunol. 16
• 作者: Kobari;Y.
• 通讯作者: Y.