Clearance of apoptotic neurons without inflammation by microglial triggering receptor expressed on myeloid cells-2.
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.
Takahashi
Kazuya
K
Neuroimmunology Unit, European Neuroscience Institute Göttingen, Germany.
Rochford
Christian D P
CD
Neumann
Harald
H
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D001927:Brain Diseases / Q000209:etiology; D002478:Cells, Cultured; D018920:Coculture Techniques; D007249:Inflammation / Q000209:etiology; D016086:Lentivirus / Q000235:genetics / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000276:immunology* / Q000378:metabolism; D009474:Neurons / Q000276:immunology*; D010587:Phagocytosis; D010766:Phosphorylation; D011971:Receptors, Immunologic / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction; D014161:Transduction, Genetic
D048868:Adaptor Proteins, Signal Transducing; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; C484963:Tyrobp protein, mouse
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