Neutralizing IL-17 protects the optic nerve from autoimmune pathology and prevents retinal nerve fiber layer atrophy during experimental autoimmune encephalomyelitis
Neutralizing IL-17 protects the optic nerve from autoimmune pathology and prevents retinal nerve fiber layer atrophy during experimental autoimmune encephalomyelitis
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DOI：
10.1016/j.jaut.2014.09.003
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发表时间：
2015-01-01
影响因子：
12.8
通讯作者：
Korn, Thomas
中科院分区：
文献类型：
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作者：
Knier, Benjamin;Rothhammer, Veit;Korn, Thomas
视神经炎是多发性硬化症（MS）的常见炎症表现。在实验性自身免疫性脑脊髓炎（EAE）中，视神经也受到影响。在这里，我们研究了视神经中的自身免疫性炎症是否与中枢神经系统（CNS）其他部位的炎症不同。在我们的研究中，视神经和大脑中的炎性浸润的特征是高比例的Ly 6 G（+）粒细胞，而在脊髓中，巨噬细胞浸润占主导地位。在疾病高峰期，IL-17 mRNA丰度在视神经中最高，与CNS的其他部分相比。视神经和脑中产生IL-17与产生IFN-γ的CD 4（+）T细胞的比例高于脊髓中的比例，并且视神经中的效应CD 4（+）T细胞比脊髓中更多地致力于Th 17转录程序。产生IL-17的γ δ T细胞而不是Ly 6 G（+）粒细胞本身有助于IL-17的产生。对小鼠眼睛的光学相干断层扫描（OCT）研究显示，在从运动症状恢复后，视网膜神经纤维层（RNFL）和神经节细胞共同层和内丛状层（GCL+）的厚度下降，表明自身免疫性炎症在EAE期间诱导视神经纤维显著萎缩。通过用抗IL-17抗体治疗来中和IL-17减少但不消除EAE的运动症状。然而，通过阻断IL-17，RNFL和GCL+萎缩被完全阻止。因此，视神经隔室特别倾向于在CNS自身免疫期间支持IL-17介导的炎症反应，并且可以通过中和IL-17来保持视网膜的结构完整性。(C)2014爱思唯尔有限公司版权所有。
Optic neuritis is a common inflammatory manifestation of multiple sclerosis (MS). In experimental autoimmune encephalomyelitis (EAE), the optic nerve is affected as well. Here, we investigated whether autoimmune inflammation in the optic nerve is distinct from inflammation in other parts of the central nervous system (CNS). In our study, inflammatory infiltrates in the optic nerve and the brain were characterized by a high fraction of Ly6G(+) granulocytes whereas in the spinal cord, macrophage infiltrates were predominant. At the peak of disease, IL-17 mRNA abundance was highest in the optic nerve as compared with other parts of the CNS. The ratio of IL-17 vs IFN-gamma producing CD4(+) T cells was higher in the optic nerve and brain than in the spinal cord and more effector CD4(+) T cells were committed to the Th17 transcriptional program in the optic nerve than in the spinal cord. IL-17 producing gamma delta T cells but rather not Ly6G(+) granulocytes themselves contributed to IL-17 production. Optical coherence tomography (OCT) studies on murine eyes revealed a decline in thickness of the retinal nerve fiber layer (RNFL) and the common layer of ganglion cells and inner plexiform layer (GCL+) after the recovery from motor symptoms indicating that autoimmune inflammation induced a significant atrophy of optic nerve fibers during EAE. Neutralization of IL-17 by treatment with anti-IL-17 antibodies reduced but did not abrogate motor symptoms of EAE. However, RNFL and GCL+ atrophy were completely prevented by blocking IL-17. Thus, the optic nerve compartment is particularly prone to support IL-17 mediated inflammatory responses during CNS autoimmunity and structural integrity of the retina can be preserved by neutralizing IL-17. (C) 2014 Elsevier Ltd. All rights reserved.