IL17A-Mediated Endothelial Breach Promotes Metastasis Formation
IL17A-Mediated Endothelial Breach Promotes Metastasis Formation
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DOI：
10.1158/2326-6066.cir-15-0154
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发表时间：
2016-01-01
影响因子：
10.1
通讯作者：
Becher, Burkhard
中科院分区：
文献类型：
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作者：
Kulig, Paulina;Burkhard, Sara;Becher, Burkhard
IL23/IL17A轴在肿瘤-免疫相互作用中的作用是有争议的。尽管一些人认为产生IL17A的T细胞(T(H)17)可以抑制肿瘤生长，但另一些人报告说IL17A和IL23促进肿瘤生长。在这里，我们系统地评估了分泌IL17A的淋巴细胞在几种肿瘤肺转移小鼠模型中的影响。基因命运图谱显示，IL17A在肺转移瘤中主要由γ-Delta T细胞分泌，而TH17细胞几乎不存在。使用不同的肿瘤模型，我们发现IL17A(-/-)小鼠持续发展较少的肺部肿瘤集落。IL17A可显著增加肺内皮细胞血管通透性及E-选择素和VCAM-1的表达。在转基因小鼠中，IL17A对内皮细胞的特异性靶向增加了肿瘤病灶的数量。此外，IL17A直接作用于肺内皮细胞导致内皮屏障完整性受损，表明IL17A通过肿瘤-内皮迁移促进肺转移的形成。(C)2015年AACR。
The role of the IL23/IL17A axis in tumor-immune interactions is a matter of controversy. Although some suggest that IL17A-producing T cells (T(H)17) can suppress tumor growth, others report that IL17A and IL23 accelerate tumor growth. Here, we systematically assessed the impact of IL17A-secreting lymphocytes in several murine models of tumor lung metastasis. Genetic fate mapping revealed that IL17A was secreted within lung metastases predominantly by gamma delta T cells, whereas TH17 cells were virtually absent. Using different tumor models, we found Il17a(-/-) mice to consistently develop fewer pulmonary tumor colonies. IL17A specifically increased blood vessel permeability and the expression of E-selectin and VCAM-1 by lung endothelial cells in vivo. In transgenic mice, specific targeting of IL17A to the endothelium increased the number of tumor foci. Moreover, the direct impact of IL17A on lung endothelial cells resulted in impaired endothelial barrier integrity, showing that IL17A promotes the formation of lung metastases through tumor-endothelial transmigration. (C) 2015 AACR.