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Oligodendrocyte-specific FADD deletion protects mice from autoimmune-mediated demyelination

(2010) JOURNAL OF IMMUNOLOGY. 185(12). p.7646-7653
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Abstract
Apoptosis of oligodendrocytes (ODCs), the myelin-producing glial cells in the CNS, plays a central role in demyelinating diseases such as multiple sclerosis and experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. To investigate the mechanism behind ODC apoptosis in EAE, we made use of conditional knockout mice lacking the adaptor protein FADD specifically in ODCs (FADD(ODC-KO)). FADD mediates apoptosis by coupling death receptors with downstream caspase activation. In line with this, ODCs from FADD(ODC-KO) mice were completely resistant to death receptor-induced apoptosis in vitro. In the EAE model, FADD(ODC-KO) mice followed an ameliorated clinical disease course in comparison with control littermates. Lymphocyte and macrophage infiltration into the spinal cord parenchyma was significantly reduced, as was the extent of demyelination and proinflammatory gene expression. Collectively, our data show that FADD is critical for ODC apoptosis and the development of autoimmune demyelinating disease.
Keywords
GROWTH-FACTOR, ENCEPHALOMYELITIS, DEATH DOMAIN, MULTIPLE-SCLEROSIS, T-CELL PROLIFERATION, CENTRAL-NERVOUS-SYSTEM, TUMOR-NECROSIS-FACTOR, APOPTOSIS, FAS, PROGRESSION

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Citation

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Chicago
Mc Guire, Conor, Thomas Volckaert, Uta Wolke, Mozes Sze, Riet De Rycke, Ari Waisman, Marco Prinz, Rudi Beyaert, Manolis Pasparakis, and Geert van Loo. 2010. “Oligodendrocyte-specific FADD Deletion Protects Mice from Autoimmune-mediated Demyelination.” Journal of Immunology 185 (12): 7646–7653.
APA
Mc Guire, C., Volckaert, T., Wolke, U., Sze, M., De Rycke, R., Waisman, A., Prinz, M., et al. (2010). Oligodendrocyte-specific FADD deletion protects mice from autoimmune-mediated demyelination. JOURNAL OF IMMUNOLOGY, 185(12), 7646–7653.
Vancouver
1.
Mc Guire C, Volckaert T, Wolke U, Sze M, De Rycke R, Waisman A, et al. Oligodendrocyte-specific FADD deletion protects mice from autoimmune-mediated demyelination. JOURNAL OF IMMUNOLOGY. 2010;185(12):7646–53.
MLA
Mc Guire, Conor, Thomas Volckaert, Uta Wolke, et al. “Oligodendrocyte-specific FADD Deletion Protects Mice from Autoimmune-mediated Demyelination.” JOURNAL OF IMMUNOLOGY 185.12 (2010): 7646–7653. Print.
@article{1089044,
  abstract     = {Apoptosis of oligodendrocytes (ODCs), the myelin-producing glial cells in the CNS, plays a central role in demyelinating diseases such as multiple sclerosis and experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. To investigate the mechanism behind ODC apoptosis in EAE, we made use of conditional knockout mice lacking the adaptor protein FADD specifically in ODCs (FADD(ODC-KO)). FADD mediates apoptosis by coupling death receptors with downstream caspase activation. In line with this, ODCs from FADD(ODC-KO) mice were completely resistant to death receptor-induced apoptosis in vitro. In the EAE model, FADD(ODC-KO) mice followed an ameliorated clinical disease course in comparison with control littermates. Lymphocyte and macrophage infiltration into the spinal cord parenchyma was significantly reduced, as was the extent of demyelination and proinflammatory gene expression. Collectively, our data show that FADD is critical for ODC apoptosis and the development of autoimmune demyelinating disease.},
  author       = {Mc Guire, Conor and Volckaert, Thomas and Wolke, Uta and Sze, Mozes and De Rycke, Riet and Waisman, Ari and Prinz, Marco and Beyaert, Rudi and Pasparakis, Manolis and van Loo, Geert},
  issn         = {0022-1767},
  journal      = {JOURNAL OF IMMUNOLOGY},
  keywords     = {GROWTH-FACTOR,ENCEPHALOMYELITIS,DEATH DOMAIN,MULTIPLE-SCLEROSIS,T-CELL PROLIFERATION,CENTRAL-NERVOUS-SYSTEM,TUMOR-NECROSIS-FACTOR,APOPTOSIS,FAS,PROGRESSION},
  language     = {eng},
  number       = {12},
  pages        = {7646--7653},
  title        = {Oligodendrocyte-specific FADD deletion protects mice from autoimmune-mediated demyelination},
  url          = {http://dx.doi.org/10.4049/jimmunol.1000930},
  volume       = {185},
  year         = {2010},
}

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