Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You and Your Team.

Learn More →

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

Clearance of apoptotic neurons without inflammation by microglial triggering receptor expressed... 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 α 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. Footnotes Abbreviations used: CCL, CC chemokine ligand; CCR7, CC chemokine receptor 7; CNS, central nervous system; ERK, extracellular signal–regulated kinase; fTREM2, Flag epitope–tagged triggering receptor expressed on myeloid cells-2 vector; GFAP, glial fibrillary acidic protein; ITAM, immunoreceptor tyrosine-based activation motif; mtDAP12, dominant negative DAP12; NOS2, nitric oxide synthase-2; PI3K, phosphatidylinositol 3-kinase; PLOSL, polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy; shControl, short hairpin control; shTREM2, short hairpin triggering receptor expressed on myeloid cells-2; TREM2, triggering receptor expressed on myeloid cells-2; wTREM2, wild-type TREM2. Submitted: 11 August 2004 Accepted: 3 January 2005 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journal of Experimental Medicine Rockefeller University Press

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

Loading next page...
 
/lp/rockefeller-university-press/clearance-of-apoptotic-neurons-without-inflammation-by-microglial-eqjFeIUzVl
Publisher
Rockefeller University Press
Copyright
© 2005 Rockefeller University Press
ISSN
0022-1007
eISSN
1540-9538
DOI
10.1084/jem.20041611
pmid
15728241
Publisher site
See Article on Publisher Site

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 α 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. Footnotes Abbreviations used: CCL, CC chemokine ligand; CCR7, CC chemokine receptor 7; CNS, central nervous system; ERK, extracellular signal–regulated kinase; fTREM2, Flag epitope–tagged triggering receptor expressed on myeloid cells-2 vector; GFAP, glial fibrillary acidic protein; ITAM, immunoreceptor tyrosine-based activation motif; mtDAP12, dominant negative DAP12; NOS2, nitric oxide synthase-2; PI3K, phosphatidylinositol 3-kinase; PLOSL, polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy; shControl, short hairpin control; shTREM2, short hairpin triggering receptor expressed on myeloid cells-2; TREM2, triggering receptor expressed on myeloid cells-2; wTREM2, wild-type TREM2. Submitted: 11 August 2004 Accepted: 3 January 2005

Journal

The Journal of Experimental MedicineRockefeller University Press

Published: Feb 21, 2005

There are no references for this article.

You’re reading a free preview. Subscribe to read the entire article.


DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Search

Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly

Organize

Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.

Access

Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

DeepDyve

Freelancer

DeepDyve

Pro

Price

FREE

$49/month
$499/year

Save searches from
Google Scholar,
PubMed

Create folders to
organize your research

Export folders, citations

Read DeepDyve articles

Abstract access only

Unlimited access to over
18 million full-text articles

Print

20 pages / month