Trebst Corinna, Staugaitis Susan M, Kivisäkk Pia, Mahad Don, Cathcart Martha K, Tucky Barbara, Wei Tao, Rani Mysore R Sandhya, Horuk Richard, Aldape Kenneth D, Pardo Carlos A, Lucchinetti Claudia F, Lassmann Hans, Ransohoff Richard M
Department of Neurosciences, The Lerner Research Institute, Cleveland, Ohio 44195, USA.
Am J Pathol. 2003 Feb;162(2):427-38. doi: 10.1016/S0002-9440(10)63837-0.
CC chemokine receptor 8 (CCR8) has been detected in vitro on type 2 helper and regulatory lymphocytes, which might exert beneficial functions in multiple sclerosis (MS) and on macrophages and microglia, possibly promoting tissue injury in MS lesions. To discriminate the relevant expression pattern in vivo, we defined the cell types that expressed CCR8 in MS lesions and determined the relationship of CCR8 expression and demyelinating activity. CCR8 was not expressed on T cells but was associated with phagocytic macrophages and activated microglia in MS lesions and directly correlated with demyelinating activity. To identify factors associated with CCR8 expression, the study was extended to other central nervous system (CNS) pathologies. CCR8 was consistently expressed on phagocytic macrophages and activated microglia in stroke and progressive multifocal leukoencephalopathy, but not expressed on microglia in pathologies that lacked phagocytic macrophages such as senile change of the Alzheimer's type. CCR8 was up-regulated by macrophage differentiation and activating stimuli in vitro. In summary CNS CCR8 expression was associated with phagocytic macrophages and activated microglial cells in human CNS diseases, suggesting that CCR8 may be a feasible target for therapeutic intervention in MS. CCR8 expression may also indicate a selective program of mononuclear phagocyte gene expression.
CC趋化因子受体8（CCR8）已在体外2型辅助性淋巴细胞和调节性淋巴细胞上检测到，这些细胞可能在多发性硬化症（MS）中发挥有益作用，在巨噬细胞和小胶质细胞上也有表达，可能促进MS病变中的组织损伤。为了区分体内相关的表达模式，我们确定了MS病变中表达CCR8的细胞类型，并确定了CCR8表达与脱髓鞘活性之间的关系。CCR8在T细胞上不表达，但与MS病变中的吞噬性巨噬细胞和活化的小胶质细胞相关，并与脱髓鞘活性直接相关。为了确定与CCR8表达相关的因素，该研究扩展到了其他中枢神经系统（CNS）疾病。CCR8在中风和进行性多灶性白质脑病的吞噬性巨噬细胞和活化的小胶质细胞上持续表达，但在缺乏吞噬性巨噬细胞的疾病（如阿尔茨海默病类型的老年变化）的小胶质细胞上不表达。CCR8在体外可被巨噬细胞分化和激活刺激上调。总之，中枢神经系统CCR8表达与人类中枢神经系统疾病中的吞噬性巨噬细胞和活化的小胶质细胞相关，这表明CCR8可能是MS治疗干预的一个可行靶点。CCR8表达也可能表明单核吞噬细胞基因表达的一个选择性程序。
