CXCR6 regulates the recruitment of pro-inflammatory IL-17A-producing T cells into atherosclerotic aortas
CXCR6 regulates the recruitment of pro-inflammatory IL-17A-producing T cells into atherosclerotic aortas
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DOI：
10.1093/intimm/dxv068
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发表时间：
2016-05-01
影响因子：
4.4
通讯作者：
Galkina, Elena V.
中科院分区：
文献类型：
--
作者：
Butcher, Matthew J.;Wu, Chih-I;Galkina, Elena V.
获得性免疫反应参与动脉粥样硬化的发生发展，而IL-17A(+)细胞在动脉粥样硬化的发生发展中起一定作用。尽管在动脉粥样硬化的小鼠动脉和人类斑块中发现了大量的CD4(+)IL-17A(+)(T-H17)和IL-17A(+)TCRγDelta(+)T细胞，但IL-17A(+)T细胞向动脉粥样硬化病变迁移的机制尚不清楚。趋化因子受体CXCR6在多种T细胞亚群上表达，在动脉粥样硬化中发挥促动脉粥样硬化作用。在这里，我们使用CXCR6缺陷(CxCr6(GFP/GFP))载脂蛋白E缺陷(APOE(-/-))小鼠来研究CXCR6在IL-17A(+)T细胞向动脉粥样硬化的募集中的作用。流式细胞仪分析显示，与年龄匹配的Cxcr6(GFP/+)APOE(-/-)主动脉相比，老年Cxcr6(GFP/GFP)APOE(-/-)主动脉中T-H17和IL-17A(+)TCRγDelta(+)T细胞减少。尽管CXCR6充足的IL-17A(+)T细胞有效地向CXCL16迁移，但缺乏CXCR6的IL-17A(+)T细胞的迁移在Transwell试验中被取消。重要的是，在短期过继转移实验中，Cxcr6(GFP/GFP)APOE(-/-)IL-17A(+)T细胞在APOE(-/-)受体的主动脉中的募集显著减少。综上所述，这些结果表明CXCR6在调节病理性T-H17和IL-17A(+)TCRγDelta(+)T细胞向动脉粥样硬化病变的募集中发挥重要作用。
The adaptive immune response is involved in the development and progression of atherosclerosis and IL-17A(+) cells play a role in this disease. Although elevated number of CD4(+) IL-17A(+) (T-h17) and IL-17A(+) TCR gamma delta(+) T cells are found within murine atherosclerotic aortas and human plaques, the mechanisms governing IL-17A(+) T-cell migration to atherosclerotic lesions are unclear. The chemokine receptor CXCR6 is expressed on several T-cell subsets and plays a pro-atherogenic role in atherosclerosis. Here, we used CXCR6-deficient (Cxcr6(GFP/GFP)) apolipoprotein E-deficient (Apoe(-/-)) mice to investigate the involvement of CXCR6 in the recruitment IL-17A(+) T cells to atherosclerotic aortas. Flow cytometric analyses revealed reductions in T-h17 and IL-17A(+) TCR gamma delta(+) T cells within aged Cxcr6(GFP/GFP)Apoe(-/-) aortas, in comparison with age-matched Cxcr6(GFP/+)Apoe(-/-) aortas. Although CXCR6-sufficient IL-17A(+) T cells efficiently migrated toward CXCL16, the migration of CXCR6-deficient IL-17A(+) T cells was abolished in transwell assays. Importantly, the recruitment of Cxcr6(GFP/GFP)Apoe(-/-) IL-17A(+) T cells into the aortas of Apoe(-/-) recipients was markedly reduced in short-term adoptive transfer experiments. Altogether these results demonstrate an important role of CXCR6 in the regulation of pathological T-h17 and IL-17A(+) TCR gamma delta(+) T-cell recruitment into atherosclerotic lesions.