Critical role of Th17 cells in inflammation and neovascularization after ischaemia
Critical role of Th17 cells in inflammation and neovascularization after ischaemia
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DOI：
10.1093/cvr/cvq397
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发表时间：
2011-05-01
影响因子：
10.8
通讯作者：
Ikeda, Uichi
中科院分区：
文献类型：
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作者：
Hata, Takeki;Takahashi, Masafumi;Ikeda, Uichi
越来越多的证据表明，CD 4（+）T细胞有助于缺血组织中的新生血管形成。然而，负责缺血后新血管形成的T细胞亚群仍有待确定。在这里，我们研究了分泌白细胞介素（IL）-17，CD 4（+）T细胞的一个新发现的子集，在小鼠后肢ischaemia.Methods和结果后，在新生血管形成的Th 17细胞的作用单侧后肢缺血野生型（WT）C57 BL/6小鼠。CD 4（+）T细胞的耗竭导致缺血肢体的血流灌注显著减少。IL-17和视黄酸受体相关孤儿受体γ t（ROR γ t）的表达在缺血肢体中上调。与WT小鼠相比，IL-17缺陷小鼠缺血肢体的血流灌注、炎性细胞浸润和血管生成细胞因子的产生显著减少。在骨髓移植实验中，骨髓细胞中特异性地缺乏IL-17减少了缺血后的新血管形成。结论Th 17细胞是一种新的血管生成性T细胞亚群，为进一步研究T细胞促进缺血后血管生成的机制提供了新的思路。
Aims Increasing evidence suggests that CD4(+) T cells contribute to neovascularization in ischaemic tissue. However, the T cell subset responsible for neovascularization after ischaemia remains to be determined. Here, we investigated the role of Th17 cells secreting interleukin (IL)-17, a newly identified subset of CD4(+) T cells, in the neovascularization after murine hindlimb ischaemia.Methods and results Unilateral hindlimb ischaemia was produced in wild-type (WT) C57BL/6 mice. Depletion of CD4(+) T cells resulted in significantly reduced blood flow perfusion in the ischaemic limbs. The expression of IL-17 and retinoic acid receptor-related orphan receptor gamma t (ROR gamma t) was up-regulated in the ischaemic limbs. IL-17-deficient mice showed a significant reduction in blood flow perfusion, inflammatory cell infiltration, and production of angiogenic cytokines in the ischaemic limbs compared with WT mice. In bone marrow transplantation experiments, the absence of IL-17 specifically in bone marrow cells diminished the neovascularization after ischaemia. Furthermore, IL-17-deficient CD4(+) T cells transferred into the ischaemic limbs of T cell-deficient athymic nude mice evoked a significantly limited neovascularization compared with WT CD4(+) T cells.Conclusion These findings identify Th17 cells as a new angiogenic T cell subset and provide new insight into the mechanism by which T cells promote neovascularization after ischaemia.