CNTF is a major protective factor in demyelinating CNS disease:: A neurotrophic cytokine as modulator in neuroinflammation
CNTF is a major protective factor in demyelinating CNS disease:: A neurotrophic cytokine as modulator in neuroinflammation
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DOI：
10.1038/nm0602-620
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发表时间：
2002-06-01
期刊：
影响因子：
82.9
通讯作者：
Gold, R
中科院分区：
文献类型：
--
作者：
Linker, RA;Mäurer, M;Gold, R
多发性硬化症（MS）是一种中枢神经系统（CNS）慢性炎症性疾病(1)。到目前为止，负责脱髓鞘的免疫机制一直是关注的焦点(2)。然而，调节轴突维持、胶质前体细胞增殖和少突胶质细胞存活的机制也可能影响疾病的预后(3)。细胞因子睫状神经营养因子（CNTF）最初被确定为分离神经元的存活因子，可促进少突胶质细胞的分化、成熟和存活（4-6）。为了研究内源性CNTF在炎性脱髓鞘疾病中的作用，我们在CNTF缺乏和野生型C57BL/6小鼠中研究了髓鞘少突胶质细胞糖蛋白（MOG）诱导的实验性自身免疫性脑脊髓炎（EAE）。cntf缺陷小鼠的疾病更为严重，恢复较差，增殖少突胶质前体细胞（OPCs）数量减少60%，少突胶质细胞凋亡率增加50%以上。此外，cntf缺陷小鼠的髓鞘空泡营养不良和轴突损伤更为严重。这些特定的病理特征可以通过抗肿瘤坏死因子- α的抗血清治疗来预防，这表明内源性CNTF可能抵消tnf - α的这种作用（参考文献7）。在这里，我们确定了在炎症环境中调节胶质细胞存活的因素，并且是EAE的结果决定因素。
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS)(1). So far, immunological mechanisms responsible for demyelination have been the focus of interest(2). However, mechanisms regulating axon maintenance as well as glial precursor-cell proliferation and oligodendrocyte survival might also influence disease outcome(3). The cytokine ciliary neurotrophic factor (CNTF), which was originally identified as a survival factor for isolated neurons, promotes differentiation, maturation and survival of oligodendrocytes(4-6). To investigate the role of endogenous CNTF in inflammatory demyelinating disease, we studied myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) in CNTF-deficient and wild-type C57BL/6 mice. Disease was more severe in CNTF-deficient mice and recovery was poor, with a 60% decrease in the number of proliferating oligodendrocyte precursor cells (OPCs) and a more than 50% increase in the rate of oligodendrocyte apoptosis. In addition, vacuolar dystrophy of myelin and axonal damage were more severe in CNTF-deficient mice. These specific pathological features could be prevented by treatment with an antiserum against tumor necrosis factor-alpha, suggesting that endogenous CNTF may counterbalance this effect of TNF-alpha (ref. 7). Here we identify a factor that modulates, in an inflammatory environment, glial cell survival and is an outcome determinant of EAE.