School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland.
Max Planck Institute of Biochemistry, Martinsried, Germany.
Immunol Rev. 2024 May;323(1):276-287. doi: 10.1111/imr.13318. Epub 2024 Mar 11.
Over the past decade, there has been a surge in discoveries of how metabolic pathways regulate immune cell function in health and disease, establishing the field of immunometabolism. Specifically, pathways such as glycolysis, the tricarboxylic acid (TCA) cycle, and those involving lipid metabolism have been implicated in regulating immune cell function. Viral infections cause immunometabolic changes which lead to antiviral immunity, but little is known about how metabolic changes regulate interferon responses. Interferons are critical cytokines in host defense, rapidly induced upon pathogen recognition, but are also involved in autoimmune diseases. This review summarizes how metabolic change impacts interferon production. We describe how glycolysis, lipid metabolism (specifically involving eicosanoids and cholesterol), and the TCA cycle-linked intermediates itaconate and fumarate impact type I interferons. Targeting these metabolic changes presents new therapeutic possibilities to modulate type I interferons during host defense or autoimmune disorders.
在过去的十年中，人们发现代谢途径如何在健康和疾病中调节免疫细胞功能，从而确立了免疫代谢领域。具体而言，糖酵解、三羧酸（TCA）循环和涉及脂质代谢的途径等已被牵涉到调节免疫细胞功能中。病毒感染会引起免疫代谢变化，从而导致抗病毒免疫，但人们对代谢变化如何调节干扰素反应知之甚少。干扰素是宿主防御中的关键细胞因子，在病原体识别后迅速诱导产生，但也与自身免疫性疾病有关。这篇综述总结了代谢变化如何影响干扰素的产生。我们描述了糖酵解、脂质代谢（特别是涉及类二十烷酸和胆固醇）以及 TCA 循环相关中间产物衣康酸和延胡索酸如何影响 I 型干扰素。针对这些代谢变化为在宿主防御或自身免疫性疾病期间调节 I 型干扰素提供了新的治疗可能性。
