TREM2-transduced myeloid precursors mediate nervous tissue debris clearance and facilitate recovery in an animal model of multiple sclerosis

被引:329
作者
Takahashi, Kazuya
Prinz, Marco
Stagi, Massimiliano
Chechneva, Olga
Neumann, Harald
机构
[1] Neural Regeneration Unit, University of Bonn Life and Brain Center, Hertie-Foundation, Bonn
[2] Neuroimmunology Unit, European Neuroscience Institute Göttingen, Göttingen
[3] Department of Neuropathology, University Hospital Göttingen, Göttingen
[4] Institute of Multiple Sclerosis Research, University of Göttingen, Hertie-Foundation
关键词
D O I
10.1371/journal.pmed.0040124
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background: In multiple sclerosis, inflammation can successfully be prevented, while promoting repair is still a major challenge. Microglial cells, the resident phagocytes of the central nervous system (CNS), are hematopoietic-derived myeloid cells and express the triggering receptor expressed on myeloid cells 2 (TREM2), an innate immune receptor. Myeloid cells are an accessible source for ex vivo gene therapy. We investigated whether myeloid precursor cells genetically modified to express TREM2 affect the disease course of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. Methods and Findings: EAE was induced in mice by immunization with a myelin autoantigen. Intravenous application of TREM2-transduced bone marrow-derived myeloid precursor cells at the EAE peak led to an amelioration of clinical symptoms, reduction in axonal damage, and prevention of further demyelination. TREM2-transduced myeloid cells applied intravenously migrated into the inflammatory spinal cord lesions of EAE-diseased mice, showed increased lysosomal and phagocytic activity, cleared degenerated myelin, and created an anti-inflammatory cytokine milieu within the CNS. Conclusions: Intravenously applied bone marrow-derived and TREM2-tranduced myeloid precursor cells limit tissue destruction and facilitate repair within the murine CNS by clearance of cellular debris during EAE. TREM2 is a new attractive target for promotion of repair and resolution of inflammation in multiple sclerosis and other neuroinflammatory diseases. © 2007 Takahashi et al.
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页码:675 / 689
页数:15
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