The adaptor Act1 is required for interleukin 17-dependent signaling associated with autoimmune and inflammatory disease
The adaptor Act1 is required for interleukin 17-dependent signaling associated with autoimmune and inflammatory disease
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DOI：
10.1038/ni1439
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发表时间：
2007-03-01
影响因子：
30.5
通讯作者：
Li, Xiaoxia
中科院分区：
文献类型：
--
作者：
Qian, Youcun;Liu, Caini;Li, Xiaoxia
产生白细胞介素 17 (IL-17) 的 T 辅助细胞与炎症和某些细菌的控制有关。我们在这里报告了接头蛋白 Act1 在 IL-17 受体 (IL-17R) 信号传导和 IL-17 依赖性免疫反应中的重要参与。用 IL-17 刺激后，Act1 募集到 IL-17R 需要 IL-17R 保守的细胞质“SEFIR”结构域，然后募集激酶 TAK1 和 E3 泛素连接酶 TRAF6，介导转录因子 NF-κ B 的“下游”激活。IL-17 诱导的炎症相关基因的表达在 Act1 缺陷的原代星形胶质细胞和肠道上皮细胞。这种减少与自身免疫性脑脊髓炎和葡聚糖硫酸钠诱导的结肠炎体内炎症性疾病的减少有关。我们的数据表明 Act1 在自身免疫和炎症性疾病的 IL-17 依赖性信号传导中至关重要。
T helper cells that produce interleukin 17 (IL-17) are associated with inflammation and the control of certain bacteria. We report here the essential involvement of the adaptor protein Act1 in IL-17 receptor (IL-17R) signaling and IL-17-dependent immune responses. After stimulation with IL-17, recruitment of Act1 to IL-17R required the IL-17R conserved cytoplasmic 'SEFIR' domain, followed by recruitment of the kinase TAK1 and E3 ubiquitin ligase TRAF6, which mediate 'downstream' activation of transcription factor NF-kappa B. IL-17-induced expression of inflammation-related genes was abolished in Act1-deficient primary astroglial and gut epithelial cells. This reduction was associated with much less inflammatory disease in vivo in both autoimmune encephalomyelitis and dextran sodium sulfate-induced colitis. Our data show that Act1 is essential in IL-17-dependent signaling in autoimmune and inflammatory disease.