{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T02:58:45Z","timestamp":1790305125457,"version":"4.1.0"},"reference-count":30,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100002241","name":"Japan Science and Technology Agency","doi-asserted-by":"publisher","award":["JPMJSP2130"],"award-info":[{"award-number":["JPMJSP2130"]}],"id":[{"id":"10.13039\/501100002241","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Genes to Cells"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Statins, inhibitors of HMG\u2010CoA reductase, exert immunomodulatory effects beyond lipid lowering, yet how they regulate T helper (Th) cell differentiation remains poorly understood. We show that fluvastatin administration to C57BL\/6 mice for 7\u2009days suppressed interferon\u2010\u03b3 and elevated interleukin\u20104 production by splenic CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells, shifting the immune balance toward Th2 without altering splenocyte numbers or major immune cell subset proportions. This effect was not shared by rosuvastatin, suggesting that lipophilicity\u2010dependent cellular uptake influences immunomodulatory potency. In\u00a0vitro experiments confirmed a direct Th2\u2010promoting action of fluvastatin on CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells. Basophils were excluded as mediating cells, as fluvastatin suppressed rather than enhanced basophil interleukin\u20104 production. Continuous fluvastatin exposure during granulocyte\u2010macrophage colony\u2010stimulating factor (GM\u2010CSF)\u2010driven dendritic cell (DC) differentiation altered the phenotype of the resulting DCs and markedly enhanced their Th2\u2010polarizing capacity in co\u2010cultures with antigen\u2010specific CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells. These functional changes were accompanied by alterations in DC surface molecule expression, although their causal contribution remains to be established. These findings indicate that continuous fluvastatin exposure during DC differentiation is associated with an altered DC phenotype and enhanced Th2\u2010polarizing capacity.\n                  <\/jats:p>","DOI":"10.1111\/gtc.70148","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:24:25Z","timestamp":1788308665000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The\n                    <scp>HMG<\/scp>\n                    \u2010\n                    <scp>CoA<\/scp>\n                    Reductase Inhibitor Fluvastatin Promotes Th2\u2010Skewed Immune Responses by Modulating Dendritic Cell Differentiation"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-4433-0428","authenticated-orcid":false,"given":"Satoshi","family":"Ishikawa","sequence":"first","affiliation":[{"name":"Department of Molecular and Cellular Health Sciences Graduate School of Pharmaceutical Sciences, Nagoya City University  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruka","family":"Mizuno","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Health Sciences Graduate School of Pharmaceutical Sciences, Nagoya City University  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanon","family":"Murase","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Health Sciences Graduate School of Pharmaceutical Sciences, Nagoya City University  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuki","family":"Sasano","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Health Sciences Graduate School of Pharmaceutical Sciences, Nagoya City University  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isamu","family":"Ogawa","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Health Sciences Graduate School of Pharmaceutical Sciences, Nagoya City University  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuka","family":"Itoh","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Health Sciences Graduate School of Pharmaceutical Sciences, Nagoya City University  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5704-0543","authenticated-orcid":false,"given":"Saotomo","family":"Itoh","sequence":"additional","affiliation":[{"name":"Laboratory of Hygienic Chemistry School of Pharmacy, Aichi Gakuin University  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4787-9430","authenticated-orcid":false,"given":"Shigeaki","family":"Hida","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Health Sciences Graduate School of Pharmaceutical Sciences, Nagoya City University  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,1]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.184.2.747"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)61350-5"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2021.687585"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2005.08.013"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2004.02.016"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.08.028"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri1839"},{"key":"e_1_2_10_9_1","first-page":"e1082","article-title":"2018 AHA\/ACC\/AACVPR\/AAPA\/ABC\/ACPM\/ADA\/AGS\/APhA\/ASPC\/NLA\/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology\/American Heart Association Task Force on Clinical Practice Guidelines","volume":"139","author":"Grundy S. 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