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Research Article

Free Access

CD70-Driven Chronic Immune Activation Is Protective against Atherosclerosis

van Olffen R.W.a · de Bruin A.M.a · Vos M.b · Staniszewska A.D.a · Hamann J.a · van Lier R.A.W.a · de Vries C.J.M.b · Nolte M.A.a

Author affiliations

Departments of aExperimental Immunology and bMedical Biochemistry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

Corresponding Author

Dr. Martijn A. Nolte

Department of Experimental Immunology

Academic Medical Center, University of Amsterdam, Meibergdreef 9

NL–1105 AZ Amsterdam (The Netherlands)

Tel. +31 20 566 2226, Fax +31 20 566 9756, E-Mail m.a.nolte@amc.nl

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J Innate Immun 2010;2:344–352

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Abstract

Chronic infection and inflammation are strongly associated with the development of atherosclerosis. To investigate whether chronic inflammation in the absence of an infectious cause also predisposes to the development of atherosclerosis, we used a mouse model in which sterile inflammation is driven by enhanced costimulation. Constitutive triggering of CD27 on T cells through overexpression of CD70 on B cells increases the numbers of IFNγ-producing effector T cells, which reduces the numbers of B cells. However, despite these pro-atherogenic features, we found that CD70-transgenic (CD70TG) mice on an ApoE*3-Leiden background were strongly protected against the induction of atherosclerotic lesions, with a normal increase in serum cholesterol level and the absence of atheroprotective antibodies. We found that circulating monocytes in CD70TG mice were activated and increased in numbers, in particular the pool of inflammatory (Ly6C+) monocytes. Importantly, monocytes from CD70TG mice had no defects in phagocytosis nor in TNFα production, but they were more prone to apoptosis, which was IFNγ-dependent. These data indicate that sterile pro-inflammatory conditions can be protective against atherosclerosis development, possibly due to a reduced viability of circulating monocytes. This unexpected outcome provides a new insight into the consequences of costimulatory signals and their impact on innate immunity.

© 2010 S. Karger AG, Basel


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Article / Publication Details

First-Page Preview
Abstract of Research Article

Received: December 23, 2009
Accepted: March 25, 2010
Published online: May 12, 2010
Issue release date: June 2010

Number of Print Pages: 9
Number of Figures: 4
Number of Tables: 0

ISSN: 1662-811X (Print)
eISSN: 1662-8128 (Online)

For additional information: https://www.karger.com/JIN


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