The protective roles of IL-18 in host defense against gastro-intestinal nematode infection by in duction of Th2 responses.

IL-18 通过诱导 Th2 反应在宿主防御胃肠道线虫感染中的保护作用。

• 批准号: 14370086
• 负责人: YOSHIMOTO Tomohiro
• 金额: $ 8.38万
• 依托单位: Hyogo College of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370086/
• 关键词: IL-18; Th2 response; mucosal mast cells; mMCP-1; gastrro-intesinal nematbde; host defense

IL-18 enhances the IL-12-deriven Th1 immune responses, but it can also stimulate Th2 immune response in the absence of IL-12. Here we show that IL-18 plus IL-2 treatment of mice induces Th2 cytokines(IL-3,IL-4,IL-9 and IL-13), intestinal mucosal mast cells(MMC) and the release of MMC-specific mouse mast cell protease-1(mMCP-1), resulting in extremely rapid expulsion of adult worms of gastrointestinal nematode Strongyloides venezuelensis(S.venezuelensis). This induction is dependent on CD4+ T cells, but not on stat6. Wild-type mice infected with S.venezuelensis L3 significantly increase in serum levels of IL-18. Furthermore, when IL-18-/-mice are infected with S.venezuelensis L3, worm expulsion is significantly delayed as compared with wild-type mice. These findings establish a role for IL-18 in immunity to gastrointestinal nematode by induction of functional intestinal MMC.

IL-18能增强IL-12诱导的Th1免疫应答，但在缺乏IL-12的情况下也能刺激Th2免疫应答。在这里，我们发现IL-18加IL-2处理小鼠可诱导Th2细胞因子(IL-3、IL-4、IL-9和IL-13)、肠粘膜肥大细胞(MMC)和MMC特异性的小鼠肥大细胞蛋白酶-1(mMCP-1)的释放，从而极快地驱逐胃肠道线虫成虫。这种诱导依赖于CD4+T细胞，而不是STAT6。野生型小鼠感染沙门氏菌L3后血清IL-18水平显著升高。此外，当IL-18-/-小鼠感染文氏链霉菌L3时，与野生型小鼠相比，驱虫显著延迟。这些发现证实了IL-18通过诱导功能性肠道MMC对胃肠道线虫的免疫作用。

项目成果

Fujimori, Y., Yoshimoto, T., et al.: "Increased expression of interleukin-18 receptor on T lymphocytes in patients with acute graft-versus-host disease after allogeneic bone marrow transplantation."J.Interferon.Cytokine.Res.. 22. 751-754 (2003)

Fujimori, Y.、Yoshimoto, T. 等人：“同种异体骨髓移植后急性移植物抗宿主病患者 T 淋巴细胞上白细胞介素 18 受体的表达增加。”J.Interferon.Cytokine.Res。

Sugimoto, T, Yoshimoto, T., et al.: "Interleukin 18 acts on memory T helper cells type 1 to induce airway inflammation and hyperresponsiveness in a naive host mouse."J.Exp.Med.. 199. 535-545 (2004)

Sugimoto, T、Yoshimoto, T. 等人：“白细胞介素 18 作用于 1 型记忆 T 辅助细胞，诱导幼稚宿主小鼠气道炎症和高反应性。”J.Exp.Med.. 199. 535-545 (

Fujimoto, M., Tsutsui, H., Xinshou, O., Tokumoto, M., watanabe, D., Shima, Y., Yoshimoto, T., Hirakata, H., Kawase, I., Nakanishi, K., Kishimoto, T., Naka, T.: "Inadequate induction of suppressor of cytokine signaling-1 causes systemic autoimmune duseases

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中西憲司, 筒井ひろ子, 善本知広: "免疫研究の最前線:IL-18とアトピー性炎症"蛋白、核酸、酵素. 38. 164-170 (2002)

Kenji Nakanishi、Hiroko Tsutsui、Tomohiro Yoshimoto：“免疫学研究前沿：IL-18 和特应性炎症”蛋白质、核酸、酶。38. 164-170 (2002)

善本知広, 中西憲司: "IL-18によるIgE産生誘導の分子機構"臨床免疫. 38. 164-170 (2002)

Tomohiro Yoshimoto、Kenji Nakanishi：“IL-18 诱导 IgE 产生的分子机制”《临床免疫学》38. 164-170 (2002)。