CXCR6 promotes atherosclerosis by supporting T cell homing, interferon gamma production and macrophage accumulation in the aortic wall (99.8)

Abstract

Abstract T cells are important in atherosclerosis, but very little is known about the mechanisms behind lymphocyte recruitment into atherosclerosis-prone aortas. We tested the hypothesis that CXCR6, a chemokine receptor that is expressed on a subset of T cells and natural killer T cells, is involved in lymphocyte homing into the aortas and modulates atherosclerosis. To investigate the role of CXCR6 in atherosclerosis, we bred CXCR6-deficient (CXCR6GFP/GFP) mice with apolipoprotein E-deficient (ApoE−/−) mice. CXCR6GFP/GFP/ApoE−/− mice fed a western diet for 17 weeks or a chow diet for 56 weeks had decreased atherosclerosis compared with ApoE−/−controls. Flow cytometry analysis of the aortas from CXCR6GFP/GFP/ApoE−/− mice showed that the reduction of atherosclerosis was accompanied by a decreased percentage of CXCR6+ T cells within the aortas. Short–term homing experiments demonstrated that CXCR6 is involved in the recruitment of CXCR6+ leukocytes into the atherosclerosis-prone aortic wall. The reduced percentage of CXCR6+ T cells within the aortas was associated with diminished production of IFNγ and reduced accumulation of CD11b+/CD68+ macrophages in the aortas. These data provide evidence for a functional role of CXCR6 in atherosclerosis by altering of the recruitment of CXCR6+ leukocytes and modulating of the local immune response within the aorta. This work is supported by NHI HL 58108, 55798 and AHA 0525532U.