Abstract |
The Fas-associated death domain (FADD) protein mediates apoptosis by coupling death receptors with the caspase cascade. Paradoxically, it also promotes cell mitosis through its C-terminal region. Apoptosis and mitosis are opposing processes that can have radically different consequences. To determine which of the FADD effects prevails in T cell-mediated autoimmune diseases, we studied myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (EAE) using mice that express a dominant-negative FADD (FADD-DN) transgene in the T cell lineage. We found that FADD blockade in T cells prevented the development of autoimmune encephalomyelitis and inhibited both Th1 and Th2 type responses. Myelin oligodendrocyte glycoprotein-specific T cell proliferation was also dramatically reduced in FADD-DN mice despite the resistance of T cells to activation-induced cell death. These results indicate that although FADD expressed by T cells is involved in regulating both mitosis and apoptosis, its effect on mitosis prevails in EAE, and that strategies inhibiting FADD functions in T cells could be effective in preventing the disease.
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Authors | Jing Sun, Brendan Hilliard, Lingyun Xu, Youhai H Chen |
Journal | Journal of immunology (Baltimore, Md. : 1950)
(J Immunol)
Vol. 175
Issue 7
Pg. 4783-8
(Oct 01 2005)
ISSN: 0022-1767 [Print] United States |
PMID | 16177127
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Adaptor Proteins, Signal Transducing
- Fadd protein, mouse
- Fas-Associated Death Domain Protein
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Topics |
- Adaptor Proteins, Signal Transducing
(antagonists & inhibitors, genetics, physiology)
- Animals
- Apoptosis
(immunology)
- Cell Differentiation
(immunology)
- Encephalomyelitis, Autoimmune, Experimental
(immunology, metabolism)
- Fas-Associated Death Domain Protein
- Lymphocyte Activation
(immunology)
- Mice
- Mice, Inbred C57BL
- Mice, Transgenic
- Mitosis
- Protein Structure, Tertiary
- T-Lymphocytes
(immunology)
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