Universität zu Köln

Mc Guire, Conor, Volckaert, Thomas, Wolke, Uta, Sze, Mozes, de Rycke, Riet, Waisman, Ari ORCID: 0000-0003-4304-8234, Prinz, Marco, Beyaert, Rudi ORCID: 0000-0002-5704-582X, Pasparakis, Manolis ORCID: 0000-0002-9870-0966 and van Loo, Geert (2010). Oligodendrocyte-Specific FADD Deletion Protects Mice from Autoimmune-Mediated Demyelination. J. Immunol., 185 (12). S. 7646 - 7654. BETHESDA: AMER ASSOC IMMUNOLOGISTS. ISSN 0022-1767

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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. The Journal of Immunology, 2010, 185: 7646-7653.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Mc Guire, Conor UNSPECIFIED UNSPECIFIED UNSPECIFIED Volckaert, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Wolke, Uta UNSPECIFIED UNSPECIFIED UNSPECIFIED Sze, Mozes UNSPECIFIED UNSPECIFIED UNSPECIFIED de Rycke, Riet UNSPECIFIED UNSPECIFIED UNSPECIFIED Waisman, Ari UNSPECIFIED orcid.org/0000-0003-4304-8234 UNSPECIFIED Prinz, Marco UNSPECIFIED UNSPECIFIED UNSPECIFIED Beyaert, Rudi UNSPECIFIED orcid.org/0000-0002-5704-582X UNSPECIFIED Pasparakis, Manolis UNSPECIFIED orcid.org/0000-0002-9870-0966 UNSPECIFIED van Loo, Geert UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-490606
DOI:	10.4049/jimmunol.1000930
Journal or Publication Title:	J. Immunol.
Volume:	185
Number:	12
Page Range:	S. 7646 - 7654
Date:	2010
Publisher:	AMER ASSOC IMMUNOLOGISTS
Place of Publication:	BETHESDA
ISSN:	0022-1767
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language TUMOR-NECROSIS-FACTOR; CENTRAL-NERVOUS-SYSTEM; T-CELL PROLIFERATION; MULTIPLE-SCLEROSIS; DEATH DOMAIN; ENCEPHALOMYELITIS; APOPTOSIS; FAS; PROGRESSION; ACTIVATION Multiple languages Immunology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/49060