Phan Anthony T, Goldrath Ananda W
Division of Biological Sciences, Molecular Biology Section, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Mol Immunol. 2015 Dec;68(2 Pt C):527-35. doi: 10.1016/j.molimm.2015.08.004. Epub 2015 Aug 19.
Resolution of infection requires the coordinated response of heterogeneous cell types to a range of physiological and pathological signals to regulate their proliferation, migration, differentiation, and effector functions. One mechanism by which immune cells integrate these signals is through modulating metabolic activity. A well-studied regulator of cellular metabolism is the hypoxia-inducible factor (HIF) family, the highly conserved central regulators of adaptation to limiting oxygen tension. HIF's regulation of cellular metabolism and a variety of effector, signaling, and trafficking molecules has made these transcription factors a recent topic of interest in T cell biology. Low oxygen availability, or hypoxia, increases expression and stabilization of HIF in immune cells, activating molecular programs both unique and common among cell types, including glycolytic metabolism. Notably, numerous oxygen-independent signals, many of which are active in T cells, also result in enhanced HIF activity. Here, we discuss both oxygen-dependent and -independent regulation of HIF activity in T cells and the resulting impacts on metabolism, differentiation, function, and immunity.
感染的消退需要多种异质性细胞类型对一系列生理和病理信号作出协调反应，以调节它们的增殖、迁移、分化和效应器功能。免疫细胞整合这些信号的一种机制是通过调节代谢活性。细胞代谢中一个经过充分研究的调节因子是缺氧诱导因子（HIF）家族，它是适应有限氧张力的高度保守的核心调节因子。HIF对细胞代谢以及多种效应器、信号分子和转运分子的调节，使这些转录因子成为近期T细胞生物学领域的研究热点。低氧可用性，即缺氧，会增加免疫细胞中HIF的表达和稳定性，激活细胞类型中独特和共有的分子程序，包括糖酵解代谢。值得注意的是，许多不依赖氧的信号，其中许多在T细胞中具有活性，也会导致HIF活性增强。在这里，我们讨论T细胞中HIF活性的氧依赖性和非氧依赖性调节，以及对代谢、分化、功能和免疫的影响。
