IL-23-Independent Induction of IL-17 from γδT Cells and Innate Lymphoid Cells Promotes Experimental Intraocular Neovascularization
IL-23-Independent Induction of IL-17 from γδT Cells and Innate Lymphoid Cells Promotes Experimental Intraocular Neovascularization
复制标题
DOI：
10.4049/jimmunol.1202495
复制
发表时间：
2013-02-15
影响因子：
4.4
通讯作者：
Yoshimura, Akihiko
中科院分区：
文献类型：
--
作者：
Hasegawa, Eiichi;Sonoda, Koh-Hei;Yoshimura, Akihiko
脉络膜新生血管(CNV)是老年性黄斑变性的特征。全基因组相关性研究表明，免疫系统参与了老年性黄斑变性的发病机制；然而，炎性细胞因子在CNV中的作用尚未确定。在这项研究中，我们证明了IL-17在激光诱导的小鼠实验性CNV中以血管内皮生长因子非依赖性的方式促进新生血管的强大潜力。眼外伤眼组织中IL-17的主要来源为浸润性的γ-Delta T细胞和Thy-1(+)的先天淋巴样细胞，而非Th17细胞。IL-23在眼内对IL-17的诱导是必不可少的。相反，我们发现IL-1β和高迁移率族蛋白1通过伽马增量T细胞强烈促进IL-17的表达。抑制IL-1β和高迁移率族蛋白1，以及耗竭γ-增量T细胞，降低IL-17水平，改善实验性CNV。我们的发现表明存在一种新的炎性细胞因子网络，它促进了眼睛中的新生血管。免疫学杂志，2013,190：1778-1787。
Choroidal neovascularization (CNV) is a characteristic of age-related macular degeneration. Genome-wide association studies have provided evidence that the immune system is involved in the pathogenesis of age-related macular degeneration; however, the role of inflammatory cytokines in CNV has not been established. In this study, we demonstrated that IL-17 had a strong potential for promoting neovascularization in a vascular endothelial growth factor-independent manner in laser-induced experimental CNV in mice. Infiltrated gamma delta T cells and Thy-1(+) innate lymphoid cells, but not Th17 cells, were the main sources of IL-17 in injured eyes. IL-23 was dispensable for IL-17 induction in the eye. Instead, we found that IL-1 beta and high-mobility group box 1 strongly promoted IL-17 expression by gamma delta T cells. Suppression of IL-1 beta and high-mobility group box 1, as well as depletion of gamma delta T cells, reduced IL-17 levels and ameliorated experimental CNV. Our findings suggest the existence of a novel inflammatory cytokine network that promotes neovascularization in the eye. The Journal of Immunology, 2013, 190: 1778-1787.