Myeloid type I interferon signaling promotes atherosclerosis by stimulating macrophage recruitment to lesions

Cell Metab. 2010 Aug 4;12(2):142-53. doi: 10.1016/j.cmet.2010.06.008.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apolipoproteins E / deficiency
  • Apolipoproteins E / genetics
  • Apolipoproteins E / metabolism
  • Atherosclerosis / immunology*
  • Cell Adhesion
  • Disease Models, Animal
  • Endothelial Cells / metabolism
  • Humans
  • Interferon-beta / toxicity*
  • Leukocytes / metabolism
  • Macrophages / drug effects
  • Macrophages / immunology*
  • Mice
  • Myeloid Cells / immunology*
  • Receptors, Lipoprotein / deficiency
  • Receptors, Lipoprotein / genetics
  • Receptors, Lipoprotein / metabolism
  • Signal Transduction*


  • Apolipoproteins E
  • IDL receptor
  • Receptors, Lipoprotein
  • Interferon-beta