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Chemokine receptor 7 knockout attenuates atherosclerotic plaque development

Authors :
Oliver Pabst
Christina Grothusen
Uwe J. F. Tietge
Maren Luchtefeld
Andreas Gagalick
Kumaravelu Jagavelu
Helmut Drexler
Bernhard Schieffer
Karsten Grote
Harald Schuett
Reinhold Förster
Center for Liver, Digestive and Metabolic Diseases (CLDM)
Lifestyle Medicine (LM)
Source :
Circulation, 122(16), 1621-U166. LIPPINCOTT WILLIAMS & WILKINS
Publication Year :
2010

Abstract

Background— Atherosclerosis is a systemic inflammatory disease characterized by the formation of atherosclerotic plaques. Both innate immunity and adaptive immunity contribute to atherogenesis, but the mode of interaction is poorly understood. Chemokine receptor 7 (CCR7) is critically involved in the transition from innate to adaptive immune activation by coordinating the migration to and positioning of antigen-presenting dendritic cells and T cells in secondary lymphoid organs. More recently, it was shown that CCR7 is also responsible for T-cell migration into inflamed tissues and T-cell egress from these tissues via the afferent lymph. Thus, we investigated the influence of a systemic CCR7 deficiency on atherogenesis in atherosclerosis-prone low-density lipoprotein receptor ( ldlr ) knockout mice. Methods and Results— CCR7 deficiency resulted in reduced atherosclerotic plaque development. CCR7 −/− T cells showed impaired entry and exit behavior from atherosclerotic lesions. Oxidized low-density lipoprotein, a key molecule for atherogenesis with antigenic features, was used to pulse dendritic cells and to expand T cells ex vivo. Adoptive transfer of C57BL/6 wild-type T cells but not ccr7 −/− -derived T cells primed with oxidized low-density lipoprotein–pulsed dendritic cells resulted in a reconstitution of atherogenesis in ccr7 −/− / ldlr −/− mice. Conclusion— These results demonstrate that both CCR7-dependent T-cell priming in secondary lymphoid organs and CCR7-dependent recirculation of T cells between secondary lymphoid organs and inflamed tissue are crucially involved in atherosclerotic plaque development.

Details

ISSN :
15244539 and 00097322
Volume :
122
Issue :
16
Database :
OpenAIRE
Journal :
Circulation
Accession number :
edsair.doi.dedup.....a8f6edec86a0d1da6a98cf1a7221b4aa