1. Chemokine receptor 7 knockout attenuates atherosclerotic plaque development
- Author
-
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), and Lifestyle Medicine (LM)
- Subjects
lymphocytes ,EXPRESSION ,CD4-Positive T-Lymphocytes ,Male ,LYMPHOID ORGANS ,Receptors, CCR7 ,OXIDIZED LDL ,Lymphocyte ,LOW-DENSITY-LIPOPROTEIN ,Aortic Diseases ,C-C chemokine receptor type 7 ,chemical and pharmacologic phenomena ,Adaptive Immunity ,DENDRITIC CELLS ,DISEASE ,lipids ,chemistry.chemical_compound ,Chemokine receptor ,Mice ,Immune system ,T-LYMPHOCYTES ,Cell Movement ,Physiology (medical) ,medicine ,PERIPHERAL-TISSUES ,Animals ,E-DEFICIENT MICE ,Mice, Knockout ,Innate immune system ,business.industry ,Macrophages ,Body Weight ,hemic and immune systems ,Acquired immune system ,Atherosclerosis ,Immunity, Innate ,Lipoproteins, LDL ,Mice, Inbred C57BL ,immune system ,Disease Models, Animal ,medicine.anatomical_structure ,chemistry ,PRIMARY IMMUNE-RESPONSE ,Low-density lipoprotein ,LDL receptor ,Immunology ,Cardiology and Cardiovascular Medicine ,business - 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.
- Published
- 2010