Multiple sclerosis: experimental models and reality.
Multiple sclerosis: experimental models and reality.
复制标题
多发性硬化症：实验模型和现实。
DOI：
10.1007/s00401-016-1631-4
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发表时间：
2017-02
影响因子：
12.7
通讯作者：
Bradl M
中科院分区：
文献类型：
--
作者：
Lassmann H;Bradl M
在介绍多发性硬化症（MS）实验研究的不同版本中，最常见的陈述之一是“多发性硬化症是一种脱髓鞘自身免疫性疾病，实验性自身免疫性脑脊髓炎（EAE）是研究其发病机制的合适模型”。然而，到目前为止，没有一个单一的实验模型涵盖了疾病的临床，病理或免疫学特征的整个谱。许多不同的模型是可用的，这被证明是非常有用的研究不同方面的炎症，脱髓鞘，髓鞘再生和神经退行性病变的中枢神经系统。然而，MS发病机制的相关性，从这样的模型的结果必须严格验证。目前的EAE模型主要基于由自身反应性CD4+ T细胞诱导的炎症，并且这些模型反映了MS的重要方面。然而，来自MS临床试验的病理学数据和结果表明，CD8+ T细胞和B淋巴细胞可能在已建立的MS中传播炎症和组织损伤中起重要作用。病毒模型可能反映MS样炎性脱髓鞘的关键特征，但是由于它们非常复杂的发病机制，涉及直接的病毒诱导和免疫介导的机制，因此难以使用。此外，病毒在MS发病机制中的作用的证据是间接的和有限的，到目前为止尚未确定MS特异性病毒感染。毒性模型对于阐明脱髓鞘和髓鞘再生机制非常有用，但不能反映MS病理学和发病机制的其他重要方面。由于所有这些原因，选择正确的实验模型来回答MS研究中的特定问题非常重要。
One of the most frequent statements, provided in different variations in the introduction of experimental studies on multiple sclerosis (MS), is that “Multiple sclerosis is a demyelinating autoimmune disease and experimental autoimmune encephalomyelitis (EAE) is a suitable model to study its pathogenesis”. However, so far, no single experimental model covers the entire spectrum of the clinical, pathological, or immunological features of the disease. Many different models are available, which proved to be highly useful for studying different aspects of inflammation, demyelination, remyelination, and neurodegeneration in the central nervous system. However, the relevance of results from such models for MS pathogenesis has to be critically validated. Current EAE models are mainly based on inflammation, induced by auto-reactive CD4+ T-cells, and these models reflect important aspects of MS. However, pathological data and results from clinical trials in MS indicate that CD8+ T-cells and B-lymphocytes may play an important role in propagating inflammation and tissue damage in established MS. Viral models may reflect key features of MS-like inflammatory demyelination, but are difficult to use due to their very complex pathogenesis, involving direct virus-induced and immune-mediated mechanisms. Furthermore, evidence for a role of viruses in MS pathogenesis is indirect and limited, and an MS-specific virus infection has not been identified so far. Toxic models are highly useful to unravel mechanisms of de- and remyelination, but do not reflect other important aspects of MS pathology and pathogenesis. For all these reasons, it is important to select the right experimental model to answer specific questions in MS research.