title: Blockade of TREM-2 exacerbates experimental autoimmune encephalomyelitis.
abstract: 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.
authors.affiliation: Bioxell SpA, Milan, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Piccio
authors.forename: Cecilia
authors.initials: C
authors.lastname: Buonsanti
authors.forename: Margherita
authors.initials: M
authors.lastname: Mariani
authors.forename: Marina
authors.initials: M
authors.lastname: Cella
authors.forename: Susan
authors.initials: S
authors.lastname: Gilfillan
authors.forename: Anne H
authors.initials: AH
authors.lastname: Cross
authors.forename: Marco
authors.initials: M
authors.lastname: Colonna
authors.forename: Paola
authors.initials: P
authors.lastname: Panina-Bordignon
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D001921:Brain / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D005455:Fluorescent Antibody Technique; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D017628:Microglia / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D011971:Receptors, Immunologic / Q000276:immunology* / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013116:Spinal Cord / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation
chemical_list: D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011971:Receptors, Immunologic; C498716:Trem2 protein, mouse