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

• 批准号: 18604003
• 负责人: HIROSE Koichi
• 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-18604003/
• 关键词: asthma; eosinophilic inflammation; IL-23; IL-17; Th17; neutrophilic inflammation

IL-23-IL-17 producing CD4^+ T cell (Th17 cell) axis seems to play an important role in the development of chronic inflammatory diseases including autoimmune diseases. In this study, we show that IL-23 and Th17 cells enhance Th2 cell-mediated allergic airway inflammation using a mouse model of asthma. We found that IL-23 mRNA was expressed in the lung of sensitized mice upon antigen inhalation. We also found that neutralization of IL-23 decreased antigen-induced eosinophil recruitment and Th2 cytokine production in the airways. Furthermore, the enforced expression of IL-23 in the airways significantly enhanced antigen-induced eosinophil recruitment and Th2 cytokine production in the airways, goblet cell hyperplasia, and airway hyperresponsiveness. Moreover, although adoptive transfer of antigen-specific Th17 cells alone did not induce eosinophil recruitment into the airways upon antigen inhalation, the cotransfer of Th17 cells with Th2 cells significantly enhanced antigen-induced, Th2 cell-mediated eosinophil recruitment into the airways. These results suggest that IL-23-Th17 cell axis upregulates Th2 cell-mediated eosinophilic airway inflammation by at least two mechanisms; IL-23 enhances the activation of Th2 cells in the effector phase and antigen-specific Th17 cells cooperate to enhance Th2 cell-mediated eosinophil recruitment into the airways.

产生 IL-23-IL-17 的 CD4^+ T 细胞（Th17 细胞）轴似乎在包括自身免疫性疾病在内的慢性炎症性疾病的发展中发挥重要作用。在这项研究中，我们使用哮喘小鼠模型证明 IL-23 和 Th17 细胞可增强 Th2 细胞介导的过敏性气道炎症。我们发现吸入抗原后致敏小鼠的肺部表达IL-23 mRNA。我们还发现 IL-23 的中和减少了气道中抗原诱导的嗜酸性粒细胞募集和 Th2 细胞因子的产生。此外，气道中IL-23的强制表达显着增强了气道中抗原诱导的嗜酸性粒细胞募集和Th2细胞因子的产生、杯状细胞增生和气道高反应性。此外，虽然单独抗原特异性Th17细胞的过继转移不会在抗原吸入时诱导嗜酸性粒细胞募集到气道中，但是Th17细胞与Th2细胞的共转移显着增强了抗原诱导的、Th2细胞介导的嗜酸性粒细胞募集到气道中。这些结果表明 IL-23-Th17 细胞轴至少通过两种机制上调 Th2 细胞介导的嗜酸性粒细胞气道炎症； IL-23 增强效应期 Th2 细胞的激活，抗原特异性 Th17 细胞协同增强 Th2 细胞介导的嗜酸性粒细胞募集到气道中。

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

Overlapping and distinct roles of STAT4 and T-bet in the regulation of T cell differentiation and allergic airway inflammation

• DOI: 10.4049/jimmunol.180.10.6656
• 发表时间: 2008-05-15
• 期刊: JOURNAL OF IMMUNOLOGY
• 影响因子: 4.4
• 作者: Furuta, Shunsuke;Kagami, Shin-ichiro;Nakajima, Hiroshi
• 通讯作者: Nakajima, Hiroshi

B and T lymphocyte attenuator inhibits antigen-induced eosinophil recruitment into the airways

B 和 T 淋巴细胞衰减剂抑制抗原诱导的嗜酸性粒细胞募集到气道中

• 发表时间: 2007
• 期刊: Int Arch Aller Imm 143
• 作者: Tamachi T;Watanabe N;Oya Y;Kagami S;Hirose K;Saito Y;Iwamoto I;Nakajima H.
• 通讯作者: Nakajima H.