The expression of"non-Th1"cytokines by"super Th1 cells"

“超级Th1细胞”表达“非Th1”细胞因子

• 批准号: 22790476
• 负责人: NAKAHIRA Masakiyo
• 金额: $ 2.58万
• 依托单位: Hyogo Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22790476/
• 关键词: 免疫学; アレルギー・ぜんそく; シグナル伝達; 発現制御

We previously demonstrated that Th1 cells gain the capacity to produce IL-13 in response to antigen, IL-2 and IL-18, and based on their unique function, we designated these activated Th1 cells as "super Th1 cells". In this project, we showed that when costimulated with anti-CD3, IL-18 and IL-4, the GATA-binding protein 3(Gata3), which is not originally expressed in Th1 cells, is induced in T-bet-expressing Th1 cells and that Gata3 is essentially required for Il13 gene expression in super Th1 cells. However, Gata3 induction is not satisfactory, and additional TCR-signaling is prerequisite for triggering IL-13 production by Gata3 plus T-bet-expressing Th1 cells. In addition, we revealed that super Th1 cells simultaneously produce IL-22, the amount of which is comparable to that of Th17 cells. Furthermore, we confirmed that when stimulated with anti-CD3, IL-2 and IL-18, Th1 cells strongly increased the expression of Rorc gene, which encodes Rorγt, "Th17-master regulator". These findings suggest that Th1 cells have the capacity to alter their cytokine profile in response to external stimuli.

我们先前证明Th 1细胞获得响应抗原、IL-2和IL-18而产生IL-13的能力，并且基于它们的独特功能，我们将这些活化的Th 1细胞命名为“超级Th 1细胞”。在这个项目中，我们表明，当与抗CD 3，IL-18和IL-4共刺激时，GATA结合蛋白3（Gata 3），这是不是最初在Th 1细胞中表达，诱导在T-bet表达的Th 1细胞和Gata 3是必需的IL-13基因在超级Th 1细胞的表达。然而，Gata 3诱导并不令人满意，并且额外的TCR信号传导是触发Gata 3加表达T-bet的Th 1细胞产生IL-13的先决条件。此外，我们发现，超级Th 1细胞同时产生IL-22，其量与Th 17细胞相当。此外，我们还证实了在抗CD 3、IL-2和IL-18刺激下，Th 1细胞Rorc基因的表达显著增加，Rorc基因编码Rorγt，即“Th 17-master regulator”。这些研究结果表明，Th 1细胞有能力改变其细胞因子谱响应外部刺激。

项目成果

IL-18で刺激したTh1細胞におけるIl13遺伝子の発現にはGATA3が必要である(Requirement of GATA binding protein 3 for Il13 gene expression in IL-18-stimulated Th1 cells)

IL-18 刺激的 Th1 细胞中 Il13 基因表达需要 GATA 结合蛋白 3

• 发表时间: 2011
• 作者: 中平雅清;中西憲司
• 通讯作者: 中西憲司

Contribution of IL-18 to eosinophilic airway inflammation induced by immunization and challenge with Staphylococcus aureus proteins

• DOI: 10.1093/intimm/dxq040
• 发表时间: 2010-07-01
• 期刊: INTERNATIONAL IMMUNOLOGY
• 影响因子: 4.4
• 作者: Kuroda-Morimoto, Mai;Tanaka, Hidehisa;Nakanishi, Kenji
• 通讯作者: Nakanishi, Kenji

IL-18で刺激したTh1細胞におけるII13遺伝子の発現にはGATA3が必要である(Requirement of GATA binding protein 3 for II13 gene expression in IL-18-stimulated Th1 cells)

IL-18 刺激的 Th1 细胞中 II13 基因表达需要 GATA 结合蛋白 3

• 发表时间: 2011
• 作者: 中平雅清;中西憲司
• 通讯作者: 中西憲司

Kenji NakanishInvolvement of Gata3 in transcriptional regulation of Il13 gene expression inIL-18-stimulated Th1 cells

Kenji Nakanish Gata3参与IL-18刺激的Th1细胞中Il13基因表达的转录调控

• 发表时间: 2010
• 作者: Hanawa-Suetsugu K;Kukimoto-Niino M;Mishima-Tsumagari C;Akasaka R;Ohsawa N;Sekine S;Ito T;Tochio N;Koshiba S;Kigawa T;Terada T;Shirouzu M;Nishikimi A;Uruno T;Katakai T;Kinashi T;Kohda D;Fukui Y;Yokoyama S;Masakiyo Nakahira
• 通讯作者: Masakiyo Nakahira

Involvement of Gata3 in transcriptional regulation of Il13 gene expression in IL-18-stimulated Th1 cells

Gata3 参与 IL-18 刺激的 Th1 细胞中 Il13 基因表达的转录调控

• 发表时间: 2010
• 作者: Masakiyo Nakahira;Kenji Nakanishi
• 通讯作者: Kenji Nakanishi