Blockade of TREM-2 exacerbates experimental autoimmune encephalomyelitis

Laura Piccio, Cecilia Buonsanti, Margherita Mariani, Marina Cella, Susan Gilfillan, Anne H. Cross, Marco Colonna, Paola Panina-Bordignon

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1290-1301
Number of pages12
JournalEuropean Journal of Immunology
Volume37
Issue number5
DOIs
Publication statusPublished - May 2007

Keywords

  • Autoimmunity
  • Experimental autoimmune encephatlitis
  • Inflammation
  • Multiple sclerosis

ASJC Scopus subject areas

  • Immunology

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