Role of IL/25 in the regulation of allergic airway inflammation

IL/25在过敏性气道炎症调节中的作用

• 批准号: 15590797
• 负责人: IWAMOTO Itsuo
• 金额: $ 2.24万
• 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: 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-15590797/
• 关键词: IL-25; Mast cells; IL-17; Eosinophils; Th2 cells; 好酸球; Th2細胞

Recently, cytokines homologous to IL-17 have been identified by database searching. Five new family members have been identified, namely IL-17B,IL-17C,IL-17D,IL-17E/IL-25,and IL-17F, in which these molecules possess 18-30% homology to IL-17. Among IL-17 family cytokines, it has been shown that the in vivo and in vitro biological activities of IL-25 are markedly different from those described for IL-17 and other IL-17 family cytokines. The expression of IL-25 results in the expansion of eosinophils through the production of IL-5 from an unidentified non-T cell population, whereas other IL-17 family cytokines induce the expansion of neutrophils. In addition, IL-25 induces elevated gene expression of IL-4 and IL-13 in multiple tissues and the resultant Th2-type immune responses, including increased serum IgE levels and pathological changes with eosinophilic infiltrates.In the present study, we first show that mast cells are also potent IL-25-producing cells. We found that when bone marrow-derived mast cells(BMMCs) were stimulated by IgE cross-linking, IL-25 mRNA was induced within 30 min in a calcineurin-dependent manner and the levels of IL-25 mRNA were comparable to that of activated Th2 cells. Production of IL-25 by mast cells was also detected at protein levels by immunoblotting.We also investigated the role of IL-25 in allergic airway inflammation. We found that IL-25 mRNA was induced in the airways in the sensitized mice upon the inhaled allergen challenge. Moreover, the enforced expression of IL-25 in the lung in CC10-IL-25 transgenic mice resulted in the enhanced antigen-induced airway inflammation. These results suggest that IL-25 is involved in the enhancement of allergic airway inflammation.

最近，已经通过数据库搜索鉴定了与IL-17同源的细胞因子。已经鉴定了五个新的家族成员，即IL-17 B、IL-17 C、IL-17 D、IL-17 E/IL-25和IL-17 F，其中这些分子与IL-17具有18-30%的同源性。在IL-17家族细胞因子中，已经显示IL-25的体内和体外生物活性与针对IL-17和其它IL-17家族细胞因子所描述的那些显著不同。IL-25的表达通过从未鉴定的非T细胞群体产生IL-5导致嗜酸性粒细胞的扩增，而其它IL-17家族细胞因子诱导嗜中性粒细胞的扩增。此外，IL-25诱导多种组织中IL-4和IL-13基因表达升高，并由此产生Th 2型免疫应答，包括血清IgE水平升高和嗜酸性粒细胞浸润的病理变化。我们发现，当骨髓来源的肥大细胞（BMMCs）刺激IgE交联，IL-25 mRNA的诱导在30分钟内在钙调神经磷酸酶依赖性的方式和IL-25 mRNA的水平相媲美的活化的Th 2细胞。免疫印迹法检测肥大细胞产生IL-25的蛋白水平，并研究IL-25在过敏性气道炎症中的作用。我们发现，IL-25 mRNA诱导在气道中的致敏小鼠吸入过敏原的挑战。此外，在CC 10-IL-25转基因小鼠中，肺中IL-25的增强表达导致抗原诱导的气道炎症增强。这些结果表明，IL-25参与了过敏性气道炎症的增强。

项目成果

Enhanced Th2 cell-mediated allergic inflammation in Tyk2-deficient mice

• DOI: 10.4049/jimmunol.170.2.1077
• 发表时间: 2003-01-15
• 期刊: JOURNAL OF IMMUNOLOGY
• 影响因子: 4.4
• 作者: Seto, Y;Nakajima, H;Iwamoto, I
• 通讯作者: Iwamoto, I

IL-4-Stat6 signaling induces trsitetraprolin expression and inhibits TNF-α production in mast cells.

IL-4-Stat6 信号传导诱导肥大细胞中 trsitetraprolin 的表达并抑制 TNF-α 的产生。

• 发表时间: 2003
• 期刊: J.Exp.Med. 198
• 作者: Suzuki K;Nakajima H;Takatori H;Saito Y;Iwamoto I.
• 通讯作者: Iwamoto I.

Stat6-protease but not Stat5-protease is inhibited by an elastase inhibitor ONO-5046.

• DOI: 10.1016/j.bbrc.2003.08.067
• 发表时间: 2003-10
• 期刊: Biochemical and biophysical research communications
• 影响因子: 3.1
• 作者: Kotaro Suzuki;H. Nakajima;K. Ikeda;T. Tamachi;T. Hiwasa;Y. Saito;I. Iwamoto

Seto Y, Nakajima H, Suto A, Saito Y, Nakayama KI, Iwamoto I.: "Enhanced Th2 cell-mediated allergic inflammation in Tyk2-deficient mice"J.Immunol.. 170. 1077-1083 (2003)

Seto Y、Nakajima H、Suto A、Saito Y、Nakayama KI、Iwamoto I.：“Tyk2 缺陷小鼠中 Th2 细胞介导的过敏性炎症增强”J.Immunol.. 170. 1077-1083 (2003)

Suzuki K, Nakajima H, Ikeda K, Maezawa Y, Saito Y, Iwamoto I: "IL-4-Stat6 signaling induces tristetraprolin expression and inhibits TNF-α production in mast cells"J.Exp.Med.. 198. 1717-1727 (2003)

Suzuki K、Nakajima H、Ikeda K、Maezawa Y、Saito Y、Iwamoto I：“IL-4-Stat6 信号传导诱导肥大细胞中 tristetraprolin 表达并抑制 TNF-α 产生”J.Exp.Med.. 198. 1717-1727 (2003)