Myeloid Type I Interferon Signaling Promotes Atherosclerosis by Stimulating Macrophage Recruitment to Lesions

P. Goossens, M.J.J. Gijbels, A. Zernecke, W. Eijgelaar, M.N. Vergouwe, I. van der Made, J. Vanderlocht, L. Beckers, W.A. Buurman, M.J.A.P. Daemen, U. Kalinke, C. Weber, E. Lutgens, M.P.J. de Winther

Research output: Contribution to journalArticleAcademicpeer-review

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.
Original languageEnglish
Pages (from-to)142-153
Number of pages12
JournalCell Metabolism
Volume12
Issue number2
DOIs
Publication statusPublished - 4 Aug 2010

Keywords

  • SYSTEMIC-LUPUS-ERYTHEMATOSUS
  • APOLIPOPROTEIN-E-DEFICIENT
  • MULTIPLE-SCLEROSIS
  • DENDRITIC CELLS
  • CROSS-TALK
  • MICE
  • BETA
  • CHEMOKINES
  • APOPTOSIS
  • SUSCEPTIBILITY

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