A novel pro-lymphangiogenic function for Th17/IL-17
A novel pro-lymphangiogenic function for Th17/IL-17
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DOI：
10.1182/blood-2011-01-332049
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发表时间：
2011-10-27
期刊：
影响因子：
20.3
通讯作者：
Dana, Reza
中科院分区：
文献类型：
--
作者：
Chauhan, Sunil K.;Jin, Yiping;Dana, Reza
Th17细胞除了具有促炎功能外，还被认为是自身免疫性疾病和恶性肿瘤中血管生成的有效诱导剂。在本研究中，我们展示了IL-17诱导淋巴管生成的不同机制。通过小鼠角膜微袋和细胞培养实验，我们的数据表明，IL-17通过诱导淋巴血管原VEGF-D的表达增加和淋巴内皮细胞的增殖，直接促进淋巴管的生长。然而，il -17诱导的血管生长主要是通过il -17应答细胞分泌IL-1 β介导的。此外，在th17显性自身免疫性眼病的临床前模型中，IL-17的体内阻断表明，角膜淋巴管生成和临床疾病进展显著减少。综上所述，我们的研究结果表明Th17/IL-17具有一种新的淋巴管生成功能，表明IL-17可以通过诱导淋巴管生成来促进免疫的进展和扩增。（血液，2011;118(17):4630-4634）
Th17 cells, in addition to their proinflammatory functions, have been recognized as potent inducers of angiogenesis in autoimmune diseases and malignancies. In the present study, we demonstrate distinct mechanisms by which IL-17 induces lymphangiogenesis. Using the mouse cornea micropocket and cell culture assays, our data demonstrate that IL-17 directly promotes growth of lymphatic vessels by inducing increased expression of prolymphangiogenic VEGF-D and proliferation of lymphatic endothelial cells. However, IL-17-induced growth of blood vessels is primarily mediated through IL-1 beta secretion by IL-17-responsive cells. Furthermore, in vivo blockade of IL-17 in a preclinical model of Th17-dominant autoimmune ocular disease demonstrates a significant reduction in the corneal lymphangiogenesis and in the progression of clinical disease. Taken together, our findings demonstrate a novel prolymphangiogenic function for Th17/IL-17, indicating that IL-17 can promote the progression andamplification of immunity in part through its induction of lymphangiogenesis. (Blood. 2011; 118(17): 4630-4634)