The roles of Dectin-1 in the development of severe asthma

Dectin-1 在严重哮喘发展中的作用

• 批准号: 20590894
• 负责人: HIROSE Koichi
• 金额: $ 3万
• 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: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20590894/
• 关键词: Dectin-1; IL-10産生性CD4陽性T細胞; STAT6; c-Maf; 気管支喘息; T-bet; ICOS-ICOSL; TGFβ; 真菌; Dection-1; β-glucan; IL-10産生性T細胞; Th17細胞

Recent evidence suggests that signals through not only Toll-like receptors(TLR) but also Dectin-1 contribute to the fine-tuning of acquired immune responses. Here, we examined the effect of Dectin-1 signaling on CD4+ T cell differentiation by using a linear form of pure β-glucan, curdlan, as a ligand. We found that curdlan instructed DCs to induce the development of IL-10-producing CD4+ T cells without the significant production of IFN-γ, IL-4, or IL-17A. We also found that IL-10-producing CD4+ T cells did not express T-bet, GATA3, RORγt, or FoxP3, but expressed c-Maf, which has been shown to activate the transcription of IL-10. Moreover, we found that STAT6 but not T-bet expressed in the CD4+ T cells is essential for the IL-10 producing T cell differentiation induced by curdlan. Taken together, these results suggest that STAT6 as well as c-Maf plays a critical role for the development of IL-10-producing CD4+ T cells in the presence of Dectin-1 activation.

最近的证据表明，不仅通过 Toll 样受体 (TLR) 的信号，而且通过 Dectin-1 的信号都有助于微调获得性免疫反应。在此，我们通过使用我们发现，curdlan 可以指导 DC 诱导产生 IL-10 的 CD4+ T 细胞的发育，但不会显着产生 IFN-γ、IL-4、我们还发现产生 IL-10 的 CD4+ T 细胞不表达 T-bet、GATA3、RORγt 或 FoxP3，但表达 c-Maf，后者已被证明可以激活 IL-10 的转录。此外，我们发现在 CD4+ T 细胞中表达的 STAT6 而不是 T-bet 对于由 curdlan 诱导的产生 IL-10 的 T 细胞分化至关重要。总而言之，这些结果表明 STAT6 以及 T-bet 都在 CD4+ T 细胞中表达。在 Dectin-1 激活的情况下，c-Maf 对于产生 IL-10 的 CD4+ T 细胞的发育起着关键作用。

项目成果

c-Maf activates the promoter and enhancer of the IL-21 gene, and TGF-P inhibits c-Maf-induced IL-21 production from CD4+ T cells

c-Maf 激活 IL-21 基因的启动子和增强子，TGF-P 抑制 c-Maf 诱导 CD4 T 细胞产生 IL-21

• 发表时间: 2010
• 期刊: J Leukoc Bio
• 作者: Hiramatsu Y;Suto A;Kashiwakuma D;Hirose K;et al.
• 通讯作者: et al.

Role of IL-23-Th17 axis in allergic airway inflammation

IL-23-Th17轴在过敏性气道炎症中的作用

• 发表时间: 2009
• 期刊: Int Aych Allergy Immunol 149
• 作者: Wakashin H;Hirose K;Iwamoto I;Nakajima H
• 通讯作者: Nakajima H

Roles of Th2 cells in IgG4-related lacrimal gland enlargement

Th2细胞在IgG4相关泪腺增大中的作用

• 发表时间: 2010
• 期刊: Int Arch Allergy Immunol
• 作者: Kanari H;Kagami S;Kashiwakuma D;Oya Y Hirose K;et al.
• 通讯作者: et al.

Protein geranylgeranylation regulates the balance between Th17 cells and Foxp3+ regulatory T cells

• DOI: 10.1093/intimm/dxp037
• 发表时间: 2009-06-01
• 期刊: INTERNATIONAL IMMUNOLOGY
• 影响因子: 4.4
• 作者: Kagami, Shin-ichiro;Owada, Takayoshi;Nakajima, Hiroshi
• 通讯作者: Nakajima, Hiroshi

B and T Lymphocyte Attenuator Suppresses IL-21 Production from Follicular Th Cells and Subsequent Humoral Immune Responses

• DOI: 10.4049/jimmunol.0903839
• 发表时间: 2010-09-01
• 期刊: JOURNAL OF IMMUNOLOGY
• 影响因子: 4.4
• 作者: Kashiwakuma, Daisuke;Suto, Akira;Nakajima, Hiroshi
• 通讯作者: Nakajima, Hiroshi