Immunohistochemical characterization of CD33 expression on microglia in Nasu-Hakola disease brains.
Immunohistochemical characterization of CD33 expression on microglia in Nasu-Hakola disease brains.
复制标题
Nasu-Hakola 病脑中小胶质细胞 CD33 表达的免疫组织化学特征。
DOI：
10.1111/neup.12222
复制
发表时间：
2015
期刊：
影响因子：
2.3
通讯作者：
Arima K
中科院分区：
文献类型：
--
作者：
Satoh J;Kino Y;Motohashi N;Ishida T;Yagishita S;Jinnai K;Arai N;Nakamagoe K;Tamaoka A;Saito Y;Arima K
Nasu-Hakola病（NHD）是一种罕见的常染色体隐性遗传病，其特征是形成多灶性骨囊肿和发展白质脑病，由DNAX活化蛋白12（DAP 12）或髓样细胞表达的触发受体2（TREM 2）的基因突变引起。尽管越来越多的证据表明NHD中小胶质细胞TREM 2/DAP 12功能缺陷，但与小胶质细胞功能障碍相关的白质脑病的分子机制仍然未知。TREM 2通过经由DAP 12的基于免疫受体酪氨酸的激活基序（ITAM）传递信号，刺激小胶质细胞的吞噬活性，并且ITAM信号传导被唾液酸结合免疫球蛋白（IG）样凝集素（Siglecs）介导的基于免疫受体酪氨酸的抑制基序（ITIM）信号传导抵消。为了研究CD 33的作用，作为小胶质细胞活化的负调节因子的Siglecs家族的成员，在NHD的病理中，我们通过免疫组织化学研究了5个NHD脑和11个对照组中的CD 33表达模式。在NHD脑中，CD 33仅在脱髓鞘白色物质病变中积累的分枝状和变形虫状小胶质细胞上鉴定，但在星形胶质细胞、少突胶质细胞或神经元中不表达。然而，CD 33免疫反应性小胶质细胞的数量在不同病例和不同病变之间表现出很大的差异，NHD和对照组大脑之间没有显著差异。这些结果并不支持表达CD 33的小胶质细胞在NHD脑白质脑病的发展中发挥核心作用的观点。
Nasu‐Hakola disease (NHD) is a rare autosomal recessive disorder, characterized by formation of multifocal bone cysts and development of leukoencephalopathy, caused by genetic mutations of either DNAX‐activation protein 12 (DAP12) or triggering receptor expressed on myeloid cells 2 (TREM2). Although increasing evidence suggests a defect in microglial TREM2/DAP12 function in NHD, the molecular mechanism underlying leukoencephalopathy with relevance to microglial dysfunction remains unknown. TREM2, by transmitting signals via the immunoreceptor tyrosine‐based activation motif (ITAM) of DAP12, stimulates phagocytic activity of microglia, and ITAM signaling is counterbalanced by sialic acid‐binding immunoglobulin (Ig)‐like lectins (Siglecs)‐mediated immunoreceptor tyrosine‐based inhibitory motif (ITIM) signaling. To investigate a role of CD33, a member of the Siglecs family acting as a negative regulator of microglia activation, in the pathology of NHD, we studied CD33 expression patterns in five NHD brains and 11 controls by immunohistochemistry. In NHD brains, CD33 was identified exclusively on ramified and amoeboid microglia accumulated in demyelinated white matter lesions but not expressed in astrocytes, oligodendrocytes, or neurons. However, the number of CD33‐immunoreactive microglia showed great variability from case to case and from lesion to lesion without significant differences between NHD and control brains. These results do not support the view that CD33‐expressing microglia play a central role in the development of leukoencephalopathy in NHD brains.