Frontiers in Physiology · Published 2026-08-04 · DOI 10.3389/fphys.2026.1859434
Omid Dadoo, B. Sumayyah H. Sokeechand, Anna Lee, Mark T. Fuller, Yu Chang David Wang, Melissa E. MacDonald, Nicole L. Batenburg, Suleiman A. Igdoura, Carl D. Richards, Ali A. Ashkar, Bernardo L. Trigatti
IntroductionInterleukin (IL)-15 is essential for the survival and maturation of natural killer (NK) and CD8+ T cells, and it directly activates macrophages.MethodsIn the present study, we examined the effects of inactivating Il-15 on atherosclerosis in apolipoprotein (apo) E-deficient mice.Results and discussionAs expected, Il-15 deficiency reduced circulating NK and CD8+ T cells in ApoE−/− mice. It also increased body weights in female but not male ApoE−/− mice and increased plasma total cholesterol levels in both. Despite this, the Il-15 knockout reduced spontaneous atherosclerotic plaque development in both male and female ApoE−/− mice (fed a normal diet) at 25 weeks of age, and in female normal diet-fed ApoE−/− mice at 15 weeks but not at 38 weeks of age. Furthermore, Il-15 knockout did not impact the levels of atherosclerosis in 25-week-old female ApoE−/− mice fed a high-fat, high-cholesterol diet for 15 weeks. However, the 6-week treatment with an antibody (M96) that blocks IL-15’s interaction with the IL-2Rβγc complex but does not interfere with its interaction with IL-15Rα reduced spontaneous atherosclerosis in female ApoE−/− mice. ApoE knockout mice in which IL-15 was inactivated or neutralized with an antibody exhibited reduced accumulation of CD11b+ and CD8+ cells within atherosclerotic plaques. These findings demonstrate that interfering with IL-15 signaling through the IL-2Rβγc complex delays spontaneous atherosclerosis development in ApoE-deficient mice.
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Dadoo, O., Sokeechand, B., Lee, A., et al. (2026). Inactivation of interleukin-15 reduces spontaneous atherosclerosis in apolipoprotein E-deficient mice. Frontiers in Physiology. https://doi.org/10.3389/fphys.2026.1859434