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PMID: 15728241 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Clearance of apoptotic neurons without inflammation by microglial triggering receptor expressed on myeloid cells-2.

The Journal of experimental medicine ·Vol. 201 ·No. 4 ·2005-02-21 ·Pages 647-57

Takahashi K, Rochford CD, Neumann H

Abstract

Elimination of apoptotic neurons without inflammation is crucial for brain tissue homeostasis, but the molecular mechanism has not been firmly established. Triggering receptor expressed on myeloid cells-2 (TREM2) is a recently identified innate immune receptor. Here, we show expression of TREM2 in microglia. TREM2 stimulation induced DAP12 phosphorylation, extracellular signal-regulated kinase phosphorylation, and cytoskeleton reorganization and increased phagocytosis. Knockdown of TREM2 in microglia inhibited phagocytosis of apoptotic neurons and increased gene transcription of tumor necrosis factor alpha and nitric oxide synthase-2, whereas overexpression of TREM2 increased phagocytosis and decreased microglial proinflammatory responses. Thus, TREM2 deficiency results in impaired clearance of apoptotic neurons and inflammation that might be responsible for the brain degeneration observed in patients with polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy/Nasu-Hakola disease.

MeSH Terms
Adaptor Proteins, Signal Transducing/genetics,immunology,metabolism Animals Apoptosis Brain Diseases/etiology Cells, Cultured Coculture Techniques Inflammation/etiology Lentivirus/genetics,metabolism Membrane Glycoproteins/deficiency,genetics,immunology Mice Mice, Inbred C57BL Microglia/immunology,metabolism Neurons/immunology Phagocytosis Phosphorylation Receptors, Immunologic/deficiency,genetics,immunology Signal Transduction Transduction, Genetic
Chemicals
Adaptor Proteins, Signal Transducing Membrane Glycoproteins Receptors, Immunologic Tyrobp protein, mouse
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Takahashi Kazuya
Neuroimmunology Unit, European Neuroscience Institute Göttingen, Germany.
Rochford Christian D P
Neumann Harald
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.20041611
Published
2005-02-21
Pages
647-57
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2213053
Subset
IM
External Links
PubMed source DOI: 10.1084/jem.20041611 PMC Full Text View journal details
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