Regional Neural Activation Defines a Gateway for Autoreactive T Cells to Cross the Blood-Brain Barrier
Regional Neural Activation Defines a Gateway for Autoreactive T Cells to Cross the Blood-Brain Barrier
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DOI：
10.1016/j.cell.2012.01.022
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发表时间：
2012-02-03
期刊：
影响因子：
64.5
通讯作者：
Murakami, Masaaki
中科院分区：
文献类型：
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作者：
Arima, Yasunobu;Harada, Masaya;Murakami, Masaaki
虽然人们认为神经激活可以影响免疫反应，但对所涉及的神经免疫相互作用知之甚少，特别是在神经免疫疾病如多发性硬化症（MS）中发生的血脑屏障免疫运输的调节剂。使用MS小鼠模型，实验性自身免疫性脑脊髓炎，我们表明，自身反应性T细胞通过第五腰椎脊髓进入中枢神经系统。该位置由相关背侧血管中趋化因子CCL 20的IL-6生物素依赖性上调来定义，这反过来又取决于重力诱导的腿部比目鱼肌对感觉神经元的激活。通过尾部悬吊损害比目鱼肌收缩足以减少局部趋化因子表达并阻断致病性T细胞进入第五腰髓，这表明区域神经免疫相互作用可能为各种神经系统疾病提供治疗靶点。
Although it is believed that neural activation can affect immune responses, very little is known about the neuroimmune interactions involved, especially the regulators of immune traffic across the blood-brain barrier which occurs in neuroimmune diseases such as multiple sclerosis (MS). Using a mouse model of MS, experimental autoimmune encephalomyelitis, we show that autoreactive T cells access the central nervous system via the fifth lumbar spinal cord. This location is defined by IL-6 amplifier-dependent upregulation of the chemokine CCL20 in associated dorsal blood vessels, which in turn depends on gravity-induced activation of sensory neurons by the soleus muscle in the leg. Impairing soleus muscle contraction by tail suspension is sufficient to reduce localized chemokine expression and block entry of pathogenic T cells at the fifth lumbar cord, suggesting that regional neuroimmune interactions may offer therapeutic targets for a variety of neurological diseases.