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.
PY - 2010
Y1 - 2010
N2 - 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
AB - 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
U2 - https://doi.org/10.1016/j.cmet.2010.06.008
DO - https://doi.org/10.1016/j.cmet.2010.06.008
M3 - Article
C2 - 20674859
SN - 1550-4131
VL - 12
SP - 142
EP - 153
JO - Cell metabolism
JF - Cell metabolism
IS - 2
ER -