TY - JOUR
T1 - Myeloid type I interferon signaling promotes atherosclerosis by stimulating macrophage recruitment to lesions
AU - Goossens, Pieter
AU - Gijbels, Marion J.J.
AU - Zernecke, Alma
AU - Eijgelaar, Wouter
AU - Vergouwe, Monique N.
AU - Van Der Made, Ingeborg
AU - Vanderlocht, Joris
AU - Beckers, Linda
AU - Buurman, Wim A.
AU - Daemen, Mat J.A.P.
AU - Kalinke, Ulrich
AU - Weber, Christian
AU - Lutgens, Esther
AU - De Winther, Menno P.J.
N1 - Funding Information:
This work was supported by the Netherlands Heart Foundation (grant no. 2005B175), Netherlands Organization for Scientific Research (ZonMW VIDI 917-66-329 to M.P.J.d.W. and VIDI 016-086-326 to E.L.), the European Union (Marie-Curie MEST-CT-2005-020706/CADRE2), the Humboldt foundation (Sofja Kovalevskaja grant to E.L.), and the European Vascular Genomics Network (EVGN). M.P.J.d.W. and E.L. are established investigators of the Netherlands Heart Foundation (2007T067 and 2009T034). We thank Lauran Stöger for critically reading the manuscript and Drs. Mathieu and Gysemans for providing the STAT1-deficient mice. We thank Chantal Pöttgens and Birgit Senden-Gijsbers for technical support.
PY - 2010/8/4
Y1 - 2010/8/4
N2 - 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.
AB - 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.
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U2 - 10.1016/j.cmet.2010.06.008
DO - 10.1016/j.cmet.2010.06.008
M3 - Article
AN - SCOPUS:77956180166
SN - 1550-4131
VL - 12
SP - 142
EP - 153
JO - Cell Metabolism
JF - Cell Metabolism
IS - 2
ER -