Reilly Nathalie A, Sonnet Friederike, Dekkers Koen F, Kwekkeboom Joanneke C, Sinke Lucy, Hilt Stan, Suleiman Hayat M, Hoeksema Marten A, Mei Hailiang, van Zwet Erik W, Everts Bart, Ioan-Facsinay Andreea, Jukema J Wouter, Heijmans Bastiaan T
Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden, the Netherlands.
Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands.
iScience. 2024 Mar 12;27(4):109496. doi: 10.1016/j.isci.2024.109496. eCollection 2024 Apr 19.
T cells are the most common immune cells in atherosclerotic plaques, and the function of T cells can be altered by fatty acids. Here, we show that pre-exposure of CD4 T cells to oleic acid, an abundant fatty acid linked to cardiovascular events, upregulates core metabolic pathways and promotes differentiation into interleukin-9 (IL-9)-producing cells upon activation. RNA sequencing of non-activated T cells reveals that oleic acid upregulates genes encoding key enzymes responsible for cholesterol and fatty acid biosynthesis. Transcription footprint analysis links these expression changes to the differentiation toward T9 cells, a pro-atherogenic subset. Spectral flow cytometry shows that pre-exposure to oleic acid results in a skew toward IL-9-producing T cells upon activation. Importantly, pharmacological inhibition of either cholesterol or fatty acid biosynthesis abolishes this effect, suggesting a beneficial role for statins beyond cholesterol lowering. Taken together, oleic acid may affect inflammatory diseases like atherosclerosis by rewiring T cell metabolism.
T细胞是动脉粥样硬化斑块中最常见的免疫细胞，脂肪酸可改变T细胞的功能。在此，我们表明，将CD4 T细胞预先暴露于油酸（一种与心血管事件相关的丰富脂肪酸），可上调核心代谢途径，并在激活后促进其分化为产生白细胞介素-9（IL-9）的细胞。对未激活的T细胞进行RNA测序发现，油酸可上调编码负责胆固醇和脂肪酸生物合成的关键酶的基因。转录足迹分析将这些表达变化与向T9细胞（一种促动脉粥样硬化亚群）的分化联系起来。光谱流式细胞术显示，预先暴露于油酸会导致激活后产生IL-9的T细胞出现偏差。重要的是，对胆固醇或脂肪酸生物合成的药理学抑制消除了这种效应，这表明他汀类药物除了降低胆固醇外还有有益作用。综上所述，油酸可能通过重塑T细胞代谢来影响动脉粥样硬化等炎症性疾病。
