{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T12:02:21Z","timestamp":1790164941310,"version":"4.1.0"},"reference-count":64,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100002996","name":"Hartstichting","doi-asserted-by":"publisher","award":["2018T051"],"award-info":[{"award-number":["2018T051"]}],"id":[{"id":"10.13039\/501100002996","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002996","name":"Hartstichting","doi-asserted-by":"publisher","award":["2019T107"],"award-info":[{"award-number":["2019T107"]}],"id":[{"id":"10.13039\/501100002996","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002996","name":"Hartstichting","doi-asserted-by":"publisher","award":["2023T138"],"award-info":[{"award-number":["2023T138"]}],"id":[{"id":"10.13039\/501100002996","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","award":["101115159"],"award-info":[{"award-number":["101115159"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Aging is a major risk factor for atherosclerosis and is accompanied by profound changes in the immune system, including effector T cell expansion, senescent cell accumulation, and increased pro\u2010inflammatory signaling. Rapamycin, a promising rejuvenation therapeutic that inhibits mTORC1 and modulates immune aging, was investigated for its potential to attenuate pro\u2010atherogenic immune responses in aged atherosclerotic mice. 80\u2010 to 90\u2010week\u2010old male\n                    <jats:italic>Ldlr<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice with established atherosclerotic lesions were treated intraperitoneally with rapamycin or control triweekly for 8\u2009weeks. Systemic and plaque immunity was assessed by flow cytometry or single\u2010cell RNA\u2010sequencing. Plaque morphology was evaluated by histology. Rapamycin treatment reduced plaque macrophage content (0.73\u2009\u00b1\u20090.07\u2009\u00d7\u200910\n                    <jats:sup>5<\/jats:sup>\n                    \u2009\u03bcm\n                    <jats:sup>2<\/jats:sup>\n                    ) compared to control (ctrl: 0.95\u2009\u00b1\u20090.09\u2009\u00d7\u200910\n                    <jats:sup>5<\/jats:sup>\n                    \u2009\u03bcm\n                    <jats:sup>2<\/jats:sup>\n                    ,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05) and decreased total T cell numbers in vascular and lymphoid tissues. This was accompanied by a shift from effector to central memory phenotypes, particularly within the CD8\n                    <jats:sup>+<\/jats:sup>\n                    compartment, and a relative enrichment of regulatory CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells (Tregs). Single\u2010cell transcriptomics of aortic Tregs revealed increased expression of suppressive genes (\n                    <jats:italic>Foxp3<\/jats:italic>\n                    ,\n                    <jats:italic>Tgfb1<\/jats:italic>\n                    ) upon rapamycin. Rapamycin also reduced T follicular helper cells, IL\u201021 expression, germinal center B cells, plasma cells, and total and oxidation\u2010specific epitope\u2010specific immunoglobulin levels. Additionally, age\u2010associated B cells were diminished in spleen and lymph nodes, reflecting a broader anti\u2010inflammatory effect on B cell immunity. Finally, aortic leukocytes displayed profoundly reduced senescent enrichment scores. Rapamycin remodels the immune landscape in aged atherosclerotic mice, promoting regulatory lymphocyte subsets and suppressing antigen\u2010driven and inflammatory immune responses. These findings highlight the potential of immune\u2010targeted rejuvenation to mitigate age\u2010related atherogenic inflammation.\n                  <\/jats:p>","DOI":"10.1111\/acel.70730","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T11:20:08Z","timestamp":1790162408000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Therapeutic Immune Reprogramming by Rapamycin Attenuates Plaque Inflammation and Lymphoid Immune Responses in Aged Atherosclerotic Mice"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3541-9912","authenticated-orcid":false,"given":"Jill","family":"de Mol","sequence":"first","affiliation":[{"name":"Division of BioTherapeutics, Leiden Academic Centre for Drug Research Leiden University  Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6976-5841","authenticated-orcid":false,"given":"Daphne H.","family":"de Korte","sequence":"additional","affiliation":[{"name":"Division of BioTherapeutics, Leiden Academic Centre for Drug Research Leiden University  Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7174-1952","authenticated-orcid":false,"given":"Marie A. C.","family":"Depuydt","sequence":"additional","affiliation":[{"name":"Division of BioTherapeutics, Leiden Academic Centre for Drug Research Leiden University  Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1181-3122","authenticated-orcid":false,"given":"Virginia","family":"Smit","sequence":"additional","affiliation":[{"name":"Division of BioTherapeutics, Leiden Academic Centre for Drug Research Leiden University  Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6027-6154","authenticated-orcid":false,"given":"Mireia N. A. Bernab\u00e9","family":"Kleijn","sequence":"additional","affiliation":[{"name":"Division of BioTherapeutics, Leiden Academic Centre for Drug Research Leiden University  Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"van Santbrink","sequence":"additional","affiliation":[{"name":"Division of BioTherapeutics, Leiden Academic Centre for Drug Research Leiden University  Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8313-7050","authenticated-orcid":false,"given":"Christoph J.","family":"Binder","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2633-6632","authenticated-orcid":false,"given":"Florentina","family":"Porsch","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank H.","family":"Schaftenaar","sequence":"additional","affiliation":[{"name":"Division of BioTherapeutics, Leiden Academic Centre for Drug Research Leiden University  Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9747-3458","authenticated-orcid":false,"given":"Amanda C.","family":"Foks","sequence":"additional","affiliation":[{"name":"Division of BioTherapeutics, Leiden Academic Centre for Drug Research Leiden University  Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,23]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"crossref","DOI":"10.1161\/CIRCRESAHA.114.302313","article-title":"Disruption of mTORC1 in Macrophages Decreases Chemokine Gene Expression and Atherosclerosis","volume":"114","author":"Ai D.","year":"2014","journal-title":"Circulation Research"},{"key":"e_1_2_10_3_1","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2019.02247","article-title":"Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? 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