HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Essential roles of the Fas-associated death domain in autoimmune encephalomyelitis.

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.
AuthorsJing Sun, Brendan Hilliard, Lingyun Xu, Youhai H Chen
JournalJournal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 175 Issue 7 Pg. 4783-8 (Oct 01 2005) ISSN: 0022-1767 [Print] United States
PMID16177127 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Adaptor Proteins, Signal Transducing
  • Fadd protein, mouse
  • Fas-Associated Death Domain Protein
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)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: