title: Immunohistochemical characterization of CD33 expression on microglia in Nasu-Hakola disease brains.
abstract: 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.
authors.affiliation: Department of Bioinformatics and Molecular Neuropathology, Meiji Pharmaceutical University, Tokyo, Japan.
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Satoh
authors.affiliation: Department of Bioinformatics and Molecular Neuropathology, Meiji Pharmaceutical University, Tokyo, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kino
authors.affiliation: Department of Psychiatry, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Motohashi
authors.affiliation: Department of Pathology and Laboratory Medicine, Kohnodai Hospital, National Center for Global Health and Medicine, Chiba, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Ishida
authors.affiliation: Department of Pathology, Kanagawa Rehabilitation Center, Kanagawa, Japan.
authors.forename: Saburo
authors.initials: S
authors.lastname: Yagishita
authors.affiliation: Department of Neurology, NHO Hyogo-Chuo Hospital, Hyogo, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Jinnai
authors.affiliation: Brain Pathology Research Center, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Arai
authors.affiliation: Department of Neurology, University of Tsukuba, Ibaraki, Japan.
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Nakamagoe
authors.affiliation: Department of Neurology, University of Tsukuba, Ibaraki, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Tamaoka
authors.affiliation: Department of Laboratory Medicine, National Center Hospital, NCNP, Tokyo, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Saito
authors.affiliation: Department of Psychiatry, Komoro Kogen Hospital, Nagano, Japan.
authors.forename: Kunimasa
authors.initials: K
authors.lastname: Arima
mesh_terms: D015153:Blotting, Western; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008060:Lipodystrophy / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D017628:Microglia / Q000378:metabolism* / Q000473:pathology*; D008875:Middle Aged; D010009:Osteochondrodysplasias / Q000378:metabolism* / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D063268:Sialic Acid Binding Ig-like Lectin 3 / Q000032:analysis / Q000096:biosynthesis*; D013344:Subacute Sclerosing Panencephalitis / Q000378:metabolism* / Q000473:pathology*
chemical_list: C571163:CD33 protein, human; D063268:Sialic Acid Binding Ig-like Lectin 3
keywords: CD33; DAP12; Nasu-Hakola disease; TREM2; microglia