Abstract
BACKGROUND - T lymphocytes are thought to be important in atherosclerosis, but very little is known about the mechanisms of lymphocyte recruitment into atherosclerosis-prone aortas. In this study we tested the hypothesis that CXCR6, a chemokine receptor that is expressed on a subset of CD4 T helper 1 cells and natural killer T cells, is involved in lymphocyte homing into the aortic wall and modulates the development and progression of atherosclerosis. METHODS AND RESULTS - To investigate the role of CXCR6 in the development and progression of atherosclerosis, we bred CXCR6-deficient (CXCR6) mice with apolipoprotein E-deficient (ApoE) mice. We found that CXCR6/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 CXCR6/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 resulted in significantly diminished production of interferon-γ and reduction of CD11b/CD68 macrophages in the aorta. CONCLUSIONS - These data provide evidence for a proatherosclerotic role of CXCR6. Absence of CXCR6 alters the recruitment of CXCR6 leukocytes and modulates the local immune response within the aortic wall.
Original language | English (US) |
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Pages (from-to) | 1801-1811 |
Number of pages | 11 |
Journal | Circulation |
Volume | 116 |
Issue number | 16 |
DOIs | |
State | Published - Oct 2007 |
Externally published | Yes |
Keywords
- Atherosclerosis
- Immune system
- Leukocytes
- Lymphocytes
- Vessels
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
- Physiology (medical)