biostudies-literatureUnknown16(1)El Bounkari OAtherosclerosis is the underlying cause of myocardial infarction and ischemic stroke. It is a lipid-triggered and cytokine/chemokine-driven arterial inflammatory condition. We identify D-dopachrome tautomerase/macrophage migration-inhibitory factor-2 (MIF-2), a paralog of the cytokine MIF, as an atypical chemokine promoting both atherosclerosis and hepatic lipid accumulation. In hyperlipidemic Apoe^-/- mice, Mif-2-deficiency and pharmacological MIF-2-blockade protect against lesion formation and vascular inflammation in early and advanced atherogenesis. MIF-2 promotes leukocyte migration, endothelial arrest, and foam-cell formation, and we identify CXCR4 as a receptor for MIF-2. Mif-2-deficiency in Apoe^-/- mice leads to decreased plasma lipid levels and suppressed hepaNature communications2297https://www.ebi.ac.uk/biostudies/studies/S-EPMC11889166biostudies-literatureAn atypical atherogenic chemokine that promotes advanced atherosclerosis and hepatic lipogenesis.PMC11889166Kempf WEHaid MKontos CBrandhofer MBucala RSchulz CZan CZarwel MHoffmann AEl Bounkari ORath DRiols FSachs NHarm TGokce OJi HMegens RTABourilhon PWeber CYang BWagner JMesserer DEbert SBugar EKapurniotu ABernhagen JJansen YDoring YAvdic MGawaz MGerra SKramer NMaegdefessel LSinitski DMilic JBartelt AWillemsen NfalseAn atypical atherogenic chemokine that promotes advanced atherosclerosis and hepatic lipogenesis.Atherosclerosis is the underlying cause of myocardial infarction and ischemic stroke. It is a lipid-triggered and cytokine/chemokine-driven arterial inflammatory condition. We identify D-dopachrome tautomerase/macrophage migration-inhibitory factor-2 (MIF-2), a paralog of the cytokine MIF, as an atypical chemokine promoting both atherosclerosis and hepatic lipid accumulation. In hyperlipidemic Apoe^-/- mice, Mif-2-deficiency and pharmacological MIF-2-blockade protect against lesion formation and vascular inflammation in early and advanced atherogenesis. MIF-2 promotes leukocyte migration, endothelial arrest, and foam-cell formation, and we identify CXCR4 as a receptor for MIF-2. Mif-2-deficiency in Apoe^-/- mice leads to decreased plasma lipid levels and suppressed hepa2025-01-01T00:00:00Z2025 Mar2026-06-01T05:06:50.549Z2025-04-04T13:11:35.598ZS-EPMC118891664005530910.1038/s41467-025-57540-z