Comprehensive Analysis of Stat5a Target Genes in Th2 Cell Differentiation

Stat5a靶基因在Th2细胞分化中的综合分析

• 批准号: 18604002
• 负责人: KAGAMI Shin-ichiro
• 金额: $ 2.61万
• 依托单位: Chiba University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18604002/
• 关键词: Stat5a; ChIP; Th2 Cells; ICOS; T cell dependent B cell responses; T_<FH> Cells; mastermind like 2; Notch receptor; クロマチン免疫沈降

Recent studies have shown the importance of Stat6-independent pathway in Th2 cell differentiation. We have previously shown that the simultaneous disruption of Stat6 and Stat5a resulted in the complete inhibition of Th2 cell differentiation and allergic airway inflammation. Therefore, Stat5a seems to be essential for Stat6-independent Th2 cell differentiation and might be a target for the treatment of allergic disorders. However, the downstream molecules of Stat5a for inducing Th2 responses are still unknown.In the present research, we attempted to identify the target genes of Stat5a by using ChIP assay. We found that Stat5a was associated in the vicinity of ICOS (inducible T-cell co-stimulator) gene, that the expression of ICOS was enhanced via Stat5a activation in IL-2 stimulated CD4+ T cells, and that the expression of ICOS on follicular helper T cells was induced by Stat5a. These results suggested that Stat5a plays an important role in mounting immune responses in part through the induction of ICOS expression.

近年来的研究表明stat6独立通路在Th2细胞分化中的重要性。我们之前已经证明Stat6和Stat5a的同时破坏导致Th2细胞分化和过敏性气道炎症的完全抑制。因此，Stat5a似乎对stat6独立的Th2细胞分化至关重要，可能是治疗过敏性疾病的靶点。然而，Stat5a诱导Th2应答的下游分子尚不清楚。在本研究中，我们尝试用ChIP法鉴定Stat5a的靶基因。我们发现Stat5a在ICOS （inducible T-cell co-stimulator）基因附近存在关联，在IL-2刺激的CD4+ T细胞中，Stat5a的激活可增强ICOS的表达，Stat5a可诱导滤泡辅助性T细胞上ICOS的表达。这些结果表明Stat5a部分通过诱导ICOS表达在免疫应答中发挥重要作用。

项目成果

T-bet inhibits both TH2 cell-mediated eosinophil recruitment and TH17 cell-mediated neutrophil recruitment into the airways

• DOI: 10.1016/j.jaci.2006.12.643
• 发表时间: 2007-03-01
• 期刊: JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
• 影响因子: 14.2
• 作者: Fujiwara, Michio;Hirose, Koichi;Nakajima, Hiroshi
• 通讯作者: Nakajima, Hiroshi

T-bet Inhibits Both Th2 Cell-mediated Eosinophil Recruitment and Th17 Cell Mediated Neutrophil Recruitment into Airways

T-bet 抑制 Th2 细胞介导的嗜酸性粒细胞募集和 Th17 细胞介导的中性粒细胞募集到气道中

• 发表时间: 2007
• 期刊: J. Allergy Clin. Immunol 119
• 作者: Fujiwara M;Hirose K;Kagami S-I;Saito Y;Iwamoto I;Nakajima H.
• 通讯作者: Nakajima H.

T-bet inhibits both Th2 cell-mediated eosinophil recruitment and Thl7 cell-mediated neutrophil recnlitment into the airways

T-bet 抑制 Th2 细胞介导的嗜酸性粒细胞募集和 Thl7 细胞介导的中性粒细胞重整进入气道

• 发表时间: 2007
• 期刊: J. Allergy Clin. Immunol. 119
• 作者: Fujiwara M;Hirose K;Kagami S;Saito Y;Iwamoto I;Nakajima H (他4名)
• 通讯作者: Nakajima H (他4名)

「研究成果報告書概要(和文)」より

摘自《研究结果报告摘要（日文）》

• 发表时间: 2005
• 作者: Kawauchi;et. al.;Nishimura et al.;Dezawa et al.;Yoshizawa et al.;星野 幹雄;星野 幹雄
• 通讯作者: 星野 幹雄

Expression of Tyk2 in Dendritic Cells is Required for IL-12, IL-23, and IFN-g Production and the Induction of Th1 Cell Differentiation

Tyk2 在树突状细胞中的表达是 IL-12、IL-23 和 IFN-g 产生以及 Th1 细胞分化诱导所必需的

• 发表时间: 2007
• 期刊: Blood 110
• 作者: Tokumasa N;Suto A;Kagami S-I;Watanabe N;Iwamoto I;Nakalima H (他4名)
• 通讯作者: Nakalima H (他4名)