{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T15:08:16Z","timestamp":1772118496569,"version":"3.50.1"},"reference-count":43,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,2,24]],"date-time":"2025-02-24T00:00:00Z","timestamp":1740355200000},"content-version":"vor","delay-in-days":23,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["19ck0106271h0003"],"award-info":[{"award-number":["19ck0106271h0003"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>The development of efficient immunosuppressants may bring significant benefits to patients after organ\/stem transplantation and those with allergies or autoimmune diseases. MEK inhibitors were originally developed as anticancer reagents, but recent reports have suggested that they may have the potential to be immunosuppressants. Trametinib is a first\u2010in\u2010class MEK inhibitor. Here, we examined the effects of trametinib on the immune system and revealed its mechanism. Trametinib suppressed both CD4 and CD8 T\u2010cell proliferation and activated T cells, which expressed CD25 and TIM3, in a dose\u2010dependent manner in vitro. Trametinib also suppressed T cell\u2010related cytokine secretion in a dose\u2010dependent manner. Notably, trametinib suppressed T cell proliferation through the induction of G1 arrest and apoptosis in stimulated T cells. In addition, trametinib induced regulatory T cells (Tregs). We confirmed that low concentrations of trametinib (1 and 10\u00a0nM) were not toxic toward splenic na\u00efve T cells and normal mouse liver cells. In this study, we demonstrated whether trametinib suppressed CD4 and CD8 T cell proliferation by inducing G1 arrest and apoptosis along with suppression of cytokine secretion.<\/jats:p>","DOI":"10.1002\/eji.202350667","type":"journal-article","created":{"date-parts":[[2025,2,26]],"date-time":"2025-02-26T04:20:44Z","timestamp":1740543644000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Trametinib Suppresses the Stimulated T Cells Through G1 Arrest and Apoptosis"],"prefix":"10.1002","volume":"55","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1003-6800","authenticated-orcid":false,"given":"Toshimasa","family":"Nakao","sequence":"first","affiliation":[{"name":"Department of Molecular\u2010Targeting Prevention Kyoto Prefectural University of Medicine  Kyoto Japan"},{"name":"Organ Transplantation Center National Center for Child Health and Development  Tokyo Japan"},{"name":"Division of Renal Surgery and 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