期刊论文详细信息
Blockade of Interleukin-17A Results in Reduced Atherosclerosis in Apolipoprotein E-Deficient Mice
Article
关键词: COLONY-STIMULATING FACTOR;    DELTA-T-CELL;    RHEUMATOID-ARTHRITIS;    AIRWAY INFLAMMATION;    INTERFERON-GAMMA;    IL-17 RECEPTOR;    TH17 CELLS;    RECRUITMENT;    IMMUNE;    ADVENTITIA;   
DOI  :  10.1161/CIRCULATIONAHA.109.924886
来源: SCIE
【 摘 要 】

Background-T cells play an important role during the immune response that accompanies atherosclerosis. To date, the role for interleukin (IL)-17A in atherogenesis is not well defined. Here, we tested the hypothesis that atherosclerosisprone conditions induce the differentiation of IL-17A-producing T cells, which in turn promote atherosclerosis. Methods and Results-IL-17A was found to be elevated in the plasma and tissues of apolipoprotein E-deficient (Apoe(-/-)) mice. IL-17A-expressing T cells were significantly increased in the aortas, spleen, and lamina propria of aged Apoe(-/-) mice compared with age-matched C57BL/6 mice. IL-17A(+) T cells resided in both adventitia and aortas of aged Apoe(-/-) mice fed a chow diet. Elevated levels of IL-17A(+) T cells were also detected in the aortas of 21-week-old Apoe(-/-) mice fed a Western diet for 15 weeks. IL-17A(+) T cells were characterized as predominantly CD4(+) T helper 17 (Th17) cells and gamma delta(+) T cells. Blockade of IL-17A in Apoe(-/-) mice by use of adenovirus-produced IL-17 receptor A reduced plaque burden in Apoe(-/-) mice fed a Western diet for 15 weeks. In addition, the treatment diminished circulating IL-6 and granulocyte colony-stimulating factor levels and limited CXCL1 expression and macrophage content within the aortas. Conversely, IL-17A treatment of whole aorta isolated from Apoe(-/-) mice promoted aortic CXCL1 expression and monocyte adhesion in an ex vivo adhesion assay. Conclusions-These results demonstrate that atherosclerosis-prone conditions induce the differentiation of IL-17A-producing T cells. IL-17A plays a proatherogenic inflammatory role during atherogenesis by promoting monocyte/macrophage recruitment into the aortic wall. (Circulation. 2010;121:1746-1755.)

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