Godfrey Wesley H, Kornberg Michael D
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Metabolites. 2020 Oct 26;10(11):426. doi: 10.3390/metabo10110426.
Immune cells undergo dramatic metabolic reprogramming in response to external stimuli. These metabolic pathways, long considered as simple housekeeping functions, are increasingly understood to critically regulate the immune response, determining the activation, differentiation, and downstream effector functions of both lymphoid and myeloid cells. Within the complex metabolic networks associated with immune activation, several enzymes play key roles in regulating inflammation and represent potential therapeutic targets in human disease. In some cases, these enzymes control flux through pathways required to meet specific energetic or metabolic demands of the immune response. In other cases, key enzymes control the concentrations of immunoactive metabolites with direct roles in signaling. Finally, and perhaps most interestingly, several metabolic enzymes have evolved moonlighting functions, with roles in the immune response that are entirely independent of their conventional enzyme activities. Here, we review key metabolic enzymes that critically regulate inflammation, highlighting mechanistic insights and opportunities for clinical intervention.
免疫细胞会因外部刺激而经历显著的代谢重编程。这些代谢途径长期以来被视为简单的维持细胞正常功能的活动，现在人们越来越认识到它们对免疫反应起着关键的调节作用，决定着淋巴细胞和髓细胞的激活、分化以及下游效应功能。在与免疫激活相关的复杂代谢网络中，几种酶在调节炎症方面发挥着关键作用，并代表了人类疾病中的潜在治疗靶点。在某些情况下，这些酶通过满足免疫反应特定能量或代谢需求所需的途径来控制通量。在其他情况下，关键酶控制具有直接信号传导作用的免疫活性代谢物的浓度。最后，也许最有趣的是，几种代谢酶具有兼职功能，在免疫反应中的作用完全独立于其传统酶活性。在这里，我们综述了对炎症起关键调节作用的关键代谢酶，强调了其作用机制的见解以及临床干预的机会。
