Involvement of Tyrosine Kinase-2 in Both the IL-12/Th1 and IL-23/Th17 Axes In Vivo
Involvement of Tyrosine Kinase-2 in Both the IL-12/Th1 and IL-23/Th17 Axes In Vivo
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DOI：
10.4049/jimmunol.1003244
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发表时间：
2011-07-01
影响因子：
4.4
通讯作者：
Matsuda, Tadashi
中科院分区：
文献类型：
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作者：
Ishizaki, Masayuki;Akimoto, Toshihiko;Matsuda, Tadashi
酪氨酸激酶-2 (Tyk2) 是 Jak 激酶家族的成员，介导由各种细胞因子触发的信号，包括 I 型 IFN、IL-12 和 IL-23。在当前的研究中，我们研究了 Tyk2 在几种 IL-12/Th1 和 IL-23/Th17 介导的实验疾病模型中的体内参与，包括甲基化 BSA 注射诱导的足垫厚度、咪喹莫特诱导的银屑病样皮肤炎症以及葡聚糖硫酸钠或 2,4,6-三硝基苯磺酸诱导的结肠炎。在这些疾病模型中，Tyk2 缺陷影响免疫和/或炎症的表型。我们的研究结果表明，Tyk2 对免疫系统的贡献比之前预期的更广泛，并表明 Tyk2 可能是靶向 IL-12/Th1 和 IL-23/Th17 轴的药物开发的重要候选者。免疫学杂志，2011，187：181-189。
Tyrosine kinase-2 (Tyk2), a member of the Jak family of kinases, mediates the signals triggered by various cytokines, including type I IFNs, IL-12, and IL-23. In the current study, we investigated the in vivo involvement of Tyk2 in several IL-12/Th1- and IL-23/Th17-mediated models of experimental diseases, including methylated BSA injection-induced footpad thickness, imiquimod-induced psoriasis-like skin inflammation, and dextran sulfate sodium-or 2,4,6-trinitrobenzene sulfonic acid-induced colitis. In these disease models, Tyk2 deficiency influenced the phenotypes in immunity and/or inflammation. Our findings demonstrate a somewhat broader contribution of Tyk2 to immune systems than previously expected and suggest that Tyk2 may represent an important candidate for drug development by targeting both the IL-12/Th1 and IL-23/Th17 axes. The Journal of Immunology, 2011, 187: 181-189.