McCandless Erin E, Klein Robyn S
Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO 63110, USA.
Expert Rev Mol Med. 2007 Jul 19;9(20):1-19. doi: 10.1017/S1462399407000397.
Autoimmune diseases of the central nervous system (CNS) involve the migration of abnormal numbers of self-directed leukocytes across the blood-brain barrier that normally separates the CNS from the immune system. The cardinal lesion associated with neuroinflammatory diseases is the perivascular infiltrate, which comprises leukocytes that have traversed the endothelium and have congregated in a subendothelial space between the endothelial-cell basement membrane and the glial limitans. The exit of mononuclear cells from this space can be beneficial, as when virus-specific lymphocytes enter the CNS for pathogen clearance, or might induce CNS damage, such as in the autoimmune disease multiple sclerosis when myelin-specific lymphocytes invade and induce demyelinating lesions. The molecular mechanisms involved in the movement of lymphocytes through these compartments involve multiple signalling pathways between these cells and the microvasculature. In this review, we discuss adhesion, costimulatory, cytokine, chemokine and signalling molecules involved in the dialogue between lymphocytes and endothelial cells that leads to inflammatory infiltrates within the CNS, and the targeting of these molecules as therapies for the treatment of multiple sclerosis.
中枢神经系统（CNS）的自身免疫性疾病涉及异常数量的自身定向白细胞穿越血脑屏障，而血脑屏障通常将中枢神经系统与免疫系统分隔开来。与神经炎症性疾病相关的主要病变是血管周围浸润，它由穿过内皮并聚集在内皮细胞基底膜和神经胶质界膜之间的内皮下空间的白细胞组成。单核细胞从这个空间逸出可能是有益的，比如当病毒特异性淋巴细胞进入中枢神经系统进行病原体清除时，但也可能导致中枢神经系统损伤，例如在自身免疫性疾病多发性硬化症中，髓鞘特异性淋巴细胞侵入并诱发脱髓鞘病变。淋巴细胞通过这些区域移动所涉及的分子机制涉及这些细胞与微血管之间的多种信号通路。在这篇综述中，我们讨论了淋巴细胞与内皮细胞之间对话中涉及的黏附分子、共刺激分子、细胞因子、趋化因子和信号分子，这些对话会导致中枢神经系统内的炎症浸润，以及将这些分子作为治疗多发性硬化症的靶点。
