Griffiths William J, Wang Yuqin
Swansea University Medical School, Swansea, Wales, United Kingdom.
J Lipid Res. 2022 Feb;63(2):100165. doi: 10.1016/j.jlr.2021.100165. Epub 2021 Dec 22.
Oxysterols, the oxidized forms of cholesterol or of its precursors, are formed in the first steps of cholesterol metabolism. Oxysterols have interested chemists, biologists, and physicians for many decades, but their exact biological relevance in vivo, other than as intermediates in bile acid biosynthesis, has long been debated. However, in the first quarter of this century, a role for side-chain oxysterols and their C-7 oxidized metabolites has been convincingly established in the immune system. 25-Hydroxycholesterol has been shown to be synthesized by macrophages in response to the activation of Toll-like receptors and to offer protection against microbial pathogens, whereas 7α,25-dihydroxycholesterol has been shown to act as a chemoattractant to lymphocytes expressing the G protein-coupled receptor Epstein-Barr virus-induced gene 2 and to be important in coordinating the action of B cells, T cells, and dendritic cells in secondary lymphoid tissue. There is a growing body of evidence that not only these two oxysterols but also many of their isomers are of importance to the proper function of the immune system. Here, we review recent findings related to the roles of oxysterols in immunology.
氧化甾醇是胆固醇或其前体的氧化形式，在胆固醇代谢的第一步中形成。几十年来，氧化甾醇一直吸引着化学家、生物学家和医生，但除了作为胆汁酸生物合成的中间体之外，它们在体内的确切生物学相关性长期以来一直存在争议。然而，在本世纪的第一个季度，侧链氧化甾醇及其C-7氧化代谢产物在免疫系统中的作用已得到令人信服的证实。已证明25-羟基胆固醇由巨噬细胞响应Toll样受体的激活而合成，并提供针对微生物病原体的保护作用，而7α,25-二羟基胆固醇已被证明可作为表达G蛋白偶联受体爱泼斯坦-巴尔病毒诱导基因2的淋巴细胞的趋化剂，并且在协调二级淋巴组织中B细胞、T细胞和树突状细胞的作用方面很重要。越来越多的证据表明，不仅这两种氧化甾醇，而且它们的许多异构体对免疫系统的正常功能都很重要。在这里，我们综述了与氧化甾醇在免疫学中的作用相关的最新发现。
