{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T04:46:20Z","timestamp":1785818780753,"version":"3.56.0"},"reference-count":55,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Interleukin (IL)-15 is essential for the survival and maturation of natural killer (NK) and CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells, and it directly activates macrophages.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In the present study, we examined the effects of inactivating\n                      <jats:italic>Il-15<\/jats:italic>\n                      on atherosclerosis in\n                      <jats:italic>apolipoprotein (apo) E<\/jats:italic>\n                      -deficient mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results and discussion<\/jats:title>\n                    <jats:p>\n                      As expected,\n                      <jats:italic>Il-15<\/jats:italic>\n                      deficiency reduced circulating NK and CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells in\n                      <jats:italic>\n                        ApoE\n                        <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      <\/jats:italic>\n                      mice. It also increased body weights in female but not male\n                      <jats:italic>\n                        ApoE\n                        <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      <\/jats:italic>\n                      mice and increased plasma total cholesterol levels in both. Despite this, the\n                      <jats:italic>Il-15<\/jats:italic>\n                      knockout reduced spontaneous atherosclerotic plaque development in both male and female\n                      <jats:italic>\n                        ApoE\n                        <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      <\/jats:italic>\n                      mice (fed a normal diet) at 25\u00a0weeks of age, and in female normal diet-fed\n                      <jats:italic>\n                        ApoE\n                        <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      <\/jats:italic>\n                      mice at 15 weeks but not at 38 weeks of age. Furthermore,\n                      <jats:italic>Il-15<\/jats:italic>\n                      knockout did not impact the levels of atherosclerosis in 25-week-old female\n                      <jats:italic>\n                        ApoE\n                        <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      <\/jats:italic>\n                      mice fed a high-fat, high-cholesterol diet for 15 weeks. However, the 6-week treatment with an antibody (M96) that blocks IL-15\u2019s interaction with the IL-2R\u03b2\u03b3\n                      <jats:sub>c<\/jats:sub>\n                      complex but does not interfere with its interaction with IL-15R\u03b1 reduced spontaneous atherosclerosis in female\n                      <jats:italic>\n                        ApoE\n                        <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      <\/jats:italic>\n                      mice.\n                      <jats:italic>ApoE<\/jats:italic>\n                      knockout mice in which IL-15 was inactivated or neutralized with an antibody exhibited reduced accumulation of CD11b\n                      <jats:sup>+<\/jats:sup>\n                      and CD8\n                      <jats:sup>+<\/jats:sup>\n                      cells within atherosclerotic plaques. These findings demonstrate that interfering with IL-15 signaling through the IL-2R\u03b2\u03b3\n                      <jats:sub>c<\/jats:sub>\n                      complex delays spontaneous atherosclerosis development in ApoE-deficient mice.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphys.2026.1859434","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T04:27:05Z","timestamp":1785817625000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Inactivation of interleukin-15 reduces spontaneous atherosclerosis in apolipoprotein E-deficient mice"],"prefix":"10.3389","volume":"17","author":[{"given":"Omid","family":"Dadoo","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Biomedical Sciences, McMaster University","place":["Hamilton, ON, Canada"]},{"name":"Thrombosis and Atherosclerosis Research Institute, Hamilton Health Sciences and McMaster University","place":["Hamilton, ON, Canada"]},{"name":"Centre for Metabolism, Obesity and Diabetes Research (MODR), McMaster University","place":["Hamilton, ON, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B. Sumayyah H.","family":"Sokeechand","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biomedical Sciences, McMaster University","place":["Hamilton, ON, Canada"]},{"name":"Thrombosis and Atherosclerosis Research Institute, Hamilton Health Sciences and McMaster University","place":["Hamilton, ON, Canada"]},{"name":"Centre for Metabolism, Obesity and Diabetes Research (MODR), McMaster University","place":["Hamilton, ON, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biomedical Sciences, McMaster University","place":["Hamilton, ON, Canada"]},{"name":"Thrombosis and Atherosclerosis Research Institute, Hamilton Health Sciences and McMaster University","place":["Hamilton, ON, Canada"]},{"name":"Centre for Metabolism, Obesity and Diabetes Research (MODR), McMaster University","place":["Hamilton, ON, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark T.","family":"Fuller","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biomedical Sciences, McMaster University","place":["Hamilton, ON, Canada"]},{"name":"Thrombosis and Atherosclerosis Research Institute, Hamilton Health Sciences and McMaster University","place":["Hamilton, ON, Canada"]},{"name":"Centre for Metabolism, Obesity and Diabetes Research (MODR), McMaster University","place":["Hamilton, ON, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu Chang David","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biomedical Sciences, McMaster University","place":["Hamilton, ON, Canada"]},{"name":"Thrombosis and Atherosclerosis Research Institute, Hamilton Health Sciences and McMaster University","place":["Hamilton, ON, Canada"]},{"name":"Centre for Metabolism, Obesity and Diabetes Research (MODR), McMaster University","place":["Hamilton, ON, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa E.","family":"MacDonald","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biomedical Sciences, McMaster University","place":["Hamilton, ON, Canada"]},{"name":"Thrombosis and Atherosclerosis Research Institute, Hamilton Health Sciences and McMaster University","place":["Hamilton, ON, Canada"]},{"name":"Centre for Metabolism, Obesity and Diabetes Research (MODR), McMaster University","place":["Hamilton, ON, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole L.","family":"Batenburg","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biomedical Sciences, McMaster University","place":["Hamilton, ON, Canada"]},{"name":"Thrombosis and Atherosclerosis Research Institute, Hamilton Health Sciences and McMaster University","place":["Hamilton, ON, Canada"]},{"name":"Centre for Metabolism, Obesity and Diabetes Research (MODR), McMaster University","place":["Hamilton, ON, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suleiman A.","family":"Igdoura","sequence":"additional","affiliation":[{"name":"Department of Biology, McMaster University","place":["Hamilton, ON, Canada"]},{"name":"Department of Pathology and Molecular Medicine, McMaster University","place":["Hamilton, ON, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl D.","family":"Richards","sequence":"additional","affiliation":[{"name":"Department of Medicine, McMaster University","place":["Hamilton, ON, Canada"]},{"name":"McMaster Immunology Research Centre, McMaster University","place":["Hamilton, ON, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali A.","family":"Ashkar","sequence":"additional","affiliation":[{"name":"Department of Medicine, McMaster University","place":["Hamilton, ON, Canada"]},{"name":"McMaster Immunology Research Centre, McMaster University","place":["Hamilton, ON, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernardo L.","family":"Trigatti","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biomedical Sciences, McMaster University","place":["Hamilton, ON, Canada"]},{"name":"Thrombosis and Atherosclerosis Research Institute, Hamilton Health Sciences and McMaster University","place":["Hamilton, ON, Canada"]},{"name":"Centre for Metabolism, Obesity and Diabetes Research (MODR), McMaster University","place":["Hamilton, ON, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"969","DOI":"10.1161\/ATVBAHA.110.207415","article-title":"Recent advances on the role of cytokines in atherosclerosis","volume":"31","author":"Ait-Oufella","year":"2011","journal-title":"Arterioscler. 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