Meningeal Mast Cells Affect Early T Cell Central Nervous System Infiltration and Blood-Brain Barrier Integrity through TNF: A Role for Neutrophil Recruitment?
Meningeal Mast Cells Affect Early T Cell Central Nervous System Infiltration and Blood-Brain Barrier Integrity through TNF: A Role for Neutrophil Recruitment?
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DOI：
10.4049/jimmunol.1000126
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发表时间：
2010-06-15
影响因子：
4.4
通讯作者：
Brown, Melissa A.
中科院分区：
文献类型：
--
作者：
Sayed, Blayne A.;Christy, Alison L.;Brown, Melissa A.
肥大细胞参与实验性自身免疫性脑脊髓炎的发病机制，这是人类脱髓鞘疾病多发性硬化症的啮齿动物模型。然而，他们的活动地点和方式是未知的。在这两种疾病中，髓磷脂特异性T细胞最初在周围淋巴器官被激活。然而，对于疾病的发生，这些细胞必须通过相对不渗透的血脑屏障进入具有免疫特权的中枢神经系统。在这项研究中，我们证明了脑膜（大脑和脊髓周围的结构）中密集的常驻肥大细胞调节基础中枢神经系统屏障功能，促进初始T细胞进入中枢神经系统。通过TNF的表达，肥大细胞募集早期中性粒细胞到中枢神经系统。我们提出中性粒细胞反过来促进血脑屏障的破坏，并与T细胞一起导致进一步的炎症细胞涌入和髓磷脂损伤。这些发现为多发性硬化症以及其他免疫介导的中枢神经系统疾病的干预提供了特定的靶点。中华免疫学杂志，2010,18(4):691 - 691。
Mast cells contribute to the pathogenesis of experimental autoimmune encephalomyelitis, a rodent model of the human demyelinating disease multiple sclerosis. Yet their site and mode of action is unknown. In both diseases, myelin-specific T cells are initially activated in peripheral lymphoid organs. However, for disease to occur, these cells must enter the immunologically privileged CNS through a breach in the relatively impermeable blood-brain barrier. In this study, we demonstrate that a dense population of resident mast cells in the meninges, structures surrounding the brain and spinal cord, regulate basal CNS barrier function, facilitating initial T cell CNS entry. Through the expression of TNF, mast cells recruit an early wave of neutrophils to the CNS. We propose that neutrophils in turn promote the blood-brain barrier breach and together with T cells lead to further inflammatory cell influx and myelin damage. These findings provide specific targets for intervention in multiple sclerosis as well as other immune-mediated CNS diseases. The Journal of Immunology, 2010, 184: 6891-6900.