mTORC1信号传导与白细胞介素-17表达：确定途径及可能的治疗靶点。
mTORC1 signaling and IL-17 expression: Defining pathways and possible therapeutic targets.
作者信息
Ren Wenkai, Yin Jie, Duan Jielin, Liu Gang, Tan Bie, Yang Guan, Wu Guoyao, Bazer Fuller W, Peng Yuanyi, Yin Yulong
机构信息
Laboratory of Animal Nutrition and Health and Key Laboratory of Agro-Ecology, Institute of Subtropical Agriculture, The Chinese Academy of Sciences, Changsha, Hunan, P. R. China.
University of the Chinese Academy of Sciences, Beijing, China.
出版信息
Eur J Immunol. 2016 Feb;46(2):291-9. doi: 10.1002/eji.201545886. Epub 2015 Dec 22.
IL-17 mediates immune responses against extracellular pathogens, and it is associated with the development and pathogenesis of various autoimmune diseases. The expression of IL-17 is regulated by various intracellular signaling cascades. Recently, it has been shown that mechanistic target of rapamycin (mTOR) signaling, comprised mainly of mTORC1 signaling, plays a critical role in IL-17 expression. Here, we review the current knowledge regarding mechanisms by which mTORC1 regulates IL-17 expression. mTORC1 positively modulates IL-17 expression through several pathways, i.e. STAT3, -HIF-1α, -S6K1, and -S6K2. Amino acids (AAs) also regulate IL-17 expression by being the energy source for Th17 cells, and by activating mTORC1 signaling. Altogether, the AA-mTORC1-IL-17 axis has broad therapeutic implications for IL-17-associated diseases, such as EAE, allergies, and colitis.
白细胞介素-17（IL-17）介导针对细胞外病原体的免疫反应，并且与多种自身免疫性疾病的发生发展及发病机制相关。IL-17的表达受多种细胞内信号级联反应调控。最近研究表明，主要由mTORC1信号组成的雷帕霉素机制性靶标（mTOR）信号在IL-17表达中起关键作用。在此，我们综述关于mTORC1调控IL-17表达机制的当前知识。mTORC1通过多种途径正向调节IL-17表达，即信号转导和转录激活因子3（STAT3）、缺氧诱导因子-1α（HIF-1α）、核糖体蛋白S6激酶1（S6K1）和核糖体蛋白S6激酶2（S6K2）。氨基酸（AAs）还通过作为辅助性T细胞17（Th17）细胞的能量来源以及激活mTORC1信号来调节IL-17表达。总之，氨基酸-mTORC1-IL-17轴对IL-17相关疾病，如实验性自身免疫性脑脊髓炎（EAE）、过敏和结肠炎具有广泛的治疗意义。
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