iScience, Volume 27, Issue 4, 12 2 2024, Pages 109496 Oleic acid triggers metabolic rewiring of T cells poising them for T helper 9 differentiation. Reilly NA, Sonnet F, Dekkers KF, Kwekkeboom JC, Sinke L, Hilt S, Suleiman HM, Hoeksema MA, Mei H, van Zwet EW, Everts B, Ioan-Facsinay A, Jukema JW, Heijmans BT
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 TH9 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.
