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

Research output: Contribution to journalArticlepeer-review

Abstract

Inflammatory cytokines are well-recognized mediators of atherosclerosis. Depending on the pathological context, type I interferons (IFNs; IFNα and IFNβ) exert either pro-or anti-inflammatory immune functions, but their exact role in atherogenesis has not been clarified. Here, we demonstrate that IFNβ enhances macrophage-endothelial cell adhesion and promotes leukocyte attraction to atherosclerosis-prone sites in mice in a chemokine-dependent manner. Moreover, IFNβ treatment accelerateslesion 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 (US)
Pages (from-to)142-153
Number of pages12
JournalCell Metabolism
Volume12
Issue number2
DOIs
StatePublished - Aug 4 2010

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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