Serafini B, Columba-Cabezas S, Di Rosa F, Aloisi F
Laboratory of Organ and System Pathophysiology, Istituto Superiore di Sanità, Rome, Italy.
Am J Pathol. 2000 Dec;157(6):1991-2002. doi: 10.1016/S0002-9440(10)64838-9.
Dendritic cells (DCs) are thought to be key elements in the initiation and maintenance of autoimmune diseases. In this study, we sought evidence that DCs recruited to the central nervous system (CNS), a site that is primarily devoid of resident DCs, play a role in the effector phase and propagation of the immune response in experimental autoimmune encephalomyelitis (EAE). After immunization of SJL mice with proteolipid protein 139-151 peptide, process-bearing cells expressing the DC markers DEC-205 and CD11c appeared early in the spinal cord. During acute, chronic, and relapsing EAE, DEC-205(+) DCs expressing a lymphostimulatory phenotype (including the mature DC marker MIDC-8, major histocompatibility complex class II, CD40, and CD86 molecules) accumulated within the CNS inflammatory cell infiltrates. More prominent infiltration of the spinal cord parenchyma by mature DCs was observed in mice with relapsing disease. Macrophage inflammatory protein 3alpha, a chemokine active on DCs and lymphocytes, and its receptor CCR6 were up-regulated in the CNS during EAE. These findings suggest that intracerebral recruitment and maturation of DCs may be crucial in the local stimulation and maintenance of autoreactive immune responses, and that therapeutic strategies aimed at manipulating DC migration could be useful in the treatment of CNS autoimmune disorders.
树突状细胞（DCs）被认为是自身免疫性疾病起始和维持的关键因素。在本研究中，我们寻找证据证明募集到中枢神经系统（CNS）的DCs（中枢神经系统主要缺乏驻留DCs）在实验性自身免疫性脑脊髓炎（EAE）的效应阶段和免疫反应传播中发挥作用。用蛋白脂质蛋白139 - 151肽免疫SJL小鼠后，表达DC标志物DEC - 205和CD11c的有突起细胞在脊髓中早期出现。在急性、慢性和复发性EAE期间，表达淋巴刺激表型（包括成熟DC标志物MIDC - 8、主要组织相容性复合体II类、CD40和CD86分子）的DEC - 205(+) DCs在CNS炎性细胞浸润中积聚。在复发性疾病小鼠中观察到成熟DCs对脊髓实质的浸润更明显。巨噬细胞炎性蛋白3α，一种对DCs和淋巴细胞有活性的趋化因子，及其受体CCR6在EAE期间在CNS中上调。这些发现表明DCs的脑内募集和成熟可能在自身反应性免疫反应的局部刺激和维持中起关键作用，并且旨在操纵DC迁移的治疗策略可能对治疗CNS自身免疫性疾病有用。
