Piccio Laura, Buonsanti Cecilia, Mariani Margherita, Cella Marina, Gilfillan Susan, Cross Anne H, Colonna Marco, Panina-Bordignon Paola
Bioxell SpA, Milan, Italy.
Eur J Immunol. 2007 May;37(5):1290-301. doi: 10.1002/eji.200636837.
Triggering receptor expressed on myeloid cells (TREM-2) is a membrane receptor associated with DAP12 that is expressed primarily in myeloid cells, including dendritic cells and microglia, and promotes fusion of osteoclast precursors into multinucleated cells. A rare autosomal recessive condition, Nasu-Hakola disease (NHD) is associated with loss-of-function mutations in DAP12 and TREM-2. The brain pathology observed in NHD patients suggests that disruption of the TREM-2/DAP12 pathway leads to neurodegeneration with demyelination and axonal loss. In this study, we have characterized TREM-2 protein expression on microglia using a newly produced monoclonal antibody directed against the mouse TREM-2 receptor. We report that TREM-2 expression is up-regulated in the spinal cord during both the early inflammatory and chronic phases of myelin oligodendrocyte glycoprotein (MOG)(35-55)peptide-induced experimental autoimmune encaphalomyelitis (EAE). We also demonstrate that TREM-2 is highly expressed on microglial cells in the central nervous system (CNS) during EAE and that blockade of TREM-2 during the effector phase of EAE results in disease exacerbation with more diffuse CNS inflammatory infiltrates and demyelination in the brain parenchyma. These results demonstrate a critical role for TREM-2 during inflammatory responses in the CNS.
髓系细胞触发受体（TREM-2）是一种与DAP12相关的膜受体，主要在髓系细胞中表达，包括树突状细胞和小胶质细胞，并促进破骨细胞前体融合为多核细胞。纳苏-哈科拉病（NHD）是一种罕见的常染色体隐性疾病，与DAP12和TREM-2的功能丧失突变有关。在NHD患者中观察到的脑部病理表明，TREM-2/DAP12通路的破坏会导致伴有脱髓鞘和轴突丢失的神经退行性变。在本研究中，我们使用新制备的针对小鼠TREM-2受体的单克隆抗体，对小胶质细胞上的TREM-2蛋白表达进行了表征。我们报告，在髓鞘少突胶质细胞糖蛋白（MOG）（35-55）肽诱导的实验性自身免疫性脑脊髓炎（EAE）的早期炎症和慢性阶段，脊髓中的TREM-2表达均上调。我们还证明，在EAE期间，TREM-2在中枢神经系统（CNS）的小胶质细胞上高度表达，并且在EAE效应阶段阻断TREM-2会导致疾病加重，脑实质中出现更弥漫的CNS炎性浸润和脱髓鞘。这些结果证明了TREM-2在CNS炎症反应中的关键作用。
