Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy.
Istituto Pasteur-Fondazione Cenci Bolognetti, Rome, Italy.
Front Immunol. 2020 Nov 3;11:584303. doi: 10.3389/fimmu.2020.584303. eCollection 2020.
The interplay between cellular stress and immune response can be variable and sometimes contradictory. The mechanisms by which stress-activated pathways regulate the inflammatory response to a pathogen, in autoimmunity or during cancer progression remain unclear in many aspects, despite our recent knowledge of the signalling and transcriptional pathways involved in these diseases. In this context, over the last decade many studies demonstrated that cholesterol metabolism is an important checkpoint for immune homeostasis and cancer progression. Indeed, cholesterol is actively metabolized and can regulate, through its mobilization and/or production of active derivatives, many aspects of immunity and inflammation. Moreover, accumulation of cholesterol has been described in cancer cells, indicating metabolic addiction. The nuclear receptors liver-X-receptors (LXRs) are important regulators of intracellular cholesterol and lipids homeostasis. They have also key regulatory roles in immune response, as they can regulate inflammation, innate and adaptive immunity. Moreover, activation of LXRs has been reported to affect the proliferation and survival of different cancer cell types that show altered metabolic pathways and accumulation of cholesterol. In this minireview we will give an overview of the recent understandings about the mechanisms through which LXRs regulate inflammation, autoimmunity, and cancer, and the therapeutic potential for future treatment of these diseases through modulation of cholesterol metabolism.
细胞应激和免疫反应之间的相互作用可能是多变的，有时甚至是矛盾的。尽管我们最近了解了这些疾病中涉及的信号和转录途径，但应激激活途径调节病原体、自身免疫或癌症进展过程中炎症反应的机制在许多方面仍不清楚。在这种情况下，在过去的十年中，许多研究表明胆固醇代谢是免疫稳态和癌症进展的重要检查点。事实上，胆固醇是被主动代谢的，并且可以通过其动员和/或产生活性衍生物来调节免疫和炎症的许多方面。此外，已经描述了胆固醇在癌细胞中的积累，表明存在代谢成瘾。肝 X 受体 (LXRs) 是细胞内胆固醇和脂质稳态的重要调节剂。它们在免疫反应中也具有关键的调节作用，因为它们可以调节炎症、先天和适应性免疫。此外，据报道，LXR 的激活会影响不同癌症细胞类型的增殖和存活，这些细胞类型表现出改变的代谢途径和胆固醇积累。在这篇简评中，我们将概述最近关于 LXR 调节炎症、自身免疫和癌症的机制的理解，以及通过调节胆固醇代谢治疗这些疾病的潜在治疗方法。
