title: Myeloid type I interferon signaling promotes atherosclerosis by stimulating macrophage recruitment to lesions.
abstract: Inflammatory cytokines are well-recognized mediators of atherosclerosis. Depending on the pathological context, type I interferons (IFNs; IFNalpha and IFNbeta) exert either pro- or anti-inflammatory immune functions, but their exact role in atherogenesis has not been clarified. Here, we demonstrate that IFNbeta enhances macrophage-endothelial cell adhesion and promotes leukocyte attraction to atherosclerosis-prone sites in mice in a chemokine-dependent manner. Moreover, IFNbeta treatment accelerates lesion formation in two different mouse models of atherosclerosis and increases macrophage accumulation in the plaques. Concomitantly, absence of endogenous type I IFN signaling in myeloid cells inhibits lesion development, protects against lesional accumulation of macrophages, and prevents necrotic core formation. Finally, we show that type I IFN signaling is upregulated in ruptured human atherosclerotic plaques. Hereby, we identify type I IFNs as proatherosclerotic cytokines that may serve as additional targets for prevention or treatment.
authors.affiliation: Department of Molecular Genetics, Cardiovascular Research Institute Maastricht, Maastricht University, 6200 MD Maastricht, The Netherlands.
authors.forename: Pieter
authors.initials: P
authors.lastname: Goossens
authors.forename: Marion J J
authors.initials: MJ
authors.lastname: Gijbels
authors.forename: Alma
authors.initials: A
authors.lastname: Zernecke
authors.forename: Wouter
authors.initials: W
authors.lastname: Eijgelaar
authors.forename: Monique N
authors.initials: MN
authors.lastname: Vergouwe
authors.forename: Ingeborg
authors.initials: I
authors.lastname: van der Made
authors.forename: Joris
authors.initials: J
authors.lastname: Vanderlocht
authors.forename: Linda
authors.initials: L
authors.lastname: Beckers
authors.forename: Wim A
authors.initials: WA
authors.lastname: Buurman
authors.forename: Mat J A P
authors.initials: MJ
authors.lastname: Daemen
authors.forename: Ulrich
authors.initials: U
authors.lastname: Kalinke
authors.forename: Christian
authors.initials: C
authors.lastname: Weber
authors.forename: Esther
authors.initials: E
authors.lastname: Lutgens
authors.forename: Menno P J
authors.initials: MP
authors.lastname: de Winther
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D050197:Atherosclerosis / Q000276:immunology*; D002448:Cell Adhesion; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism; D006801:Humans; D016899:Interferon-beta / Q000633:toxicity*; D007962:Leukocytes / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D022423:Myeloid Cells / Q000276:immunology*; D018110:Receptors, Lipoprotein / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D001057:Apolipoproteins E; C050009:IDL receptor; D018110:Receptors, Lipoprotein; D016899:Interferon-beta