mTORC1 and mTORC2 as regulators of cell metabolism in immunity.

mTORC1 and mTORC2 as regulators of cell metabolism in immunity.
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DOI:
10.1002/1873-3468.12711
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发表时间:
2017-10
期刊:
影响因子:
3.5
通讯作者:
Weichhart T
Weichhart T
中科院分区:
生物学3区
文献类型:
--
作者:
Linke M;Fritsch SD;Sukhbaatar N;Hengstschläger M;Weichhart T

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雷帕霉素途径的机制靶点(MTOR)是一条进化保守的信号通路,它感知细胞内外的营养物质、生长因子和病原体相关的分子模式,以调节先天性和获得性免疫细胞群的功能。在本文中,我们主要介绍mTOR复合体1(MTORC1)和mTORC2在调节免疫细胞能量代谢中的作用,以调节和支持免疫应答。在这方面,mTORC1和mTORC2通常通过刺激蛋白质合成、糖酵解、线粒体功能和脂肪合成来促进合成代谢反应,从而影响增殖和存活、效应和记忆反应、先天训练和耐受以及造血干细胞的维持和分化。MTOR的失活可以在免疫激活后恢复细胞内稳态,并优化抗原提呈和记忆T细胞的生成。这些发现表明,mTOR通路通过调节细胞代谢反应来整合环境和细胞能量状态的时空信息,从而指导免疫细胞的激活。阐明免疫反应的代谢控制机制将有助于对免疫系统的系统了解。
The mechanistic target of rapamycin (mTOR) pathway is an evolutionary conserved signaling pathway that senses intra- and extracellular nutrients, growth factors, and pathogen-associated molecular patterns to regulate the function of innate and adaptive immune cell populations. In this review, we focus on the role of the mTOR complex 1 (mTORC1) and mTORC2 in the regulation of the cellular energy metabolism of these immune cells to regulate and support immune responses. In this regard, mTORC1 and mTORC2 generally promote an anabolic response by stimulating protein synthesis, glycolysis, mitochondrial functions, and lipid synthesis to influence proliferation and survival, effector and memory responses, innate training and tolerance as well as hematopoietic stem cell maintenance and differentiation. Deactivation of mTOR restores cell homeostasis after immune activation and optimizes antigen presentation and memory T-cell generation. These findings show that the mTOR pathway integrates spatiotemporal information of the environmental and cellular energy status by regulating cellular metabolic responses to guide immune cell activation. Elucidation of the metabolic control mechanisms of immune responses will help to generate a systemic understanding of the immune system.
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