The role of Fas and IL-6 in experimental autoimmune encephalomyelitis

• Applicant: Professor Dr. Ari Waisman
• Subject Area: Biochemistry
• Term: from 2002 to 2005
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5374256

Multiple sclerosis (MS), an inflammatory disease that affects nearly one million people worldwide, arises when the immune system mistakenly attacks self molecules within the white matter of the brain and spinal cord. The etiology of MS is so far unknown. Experimental autoimmune encephalomyelitis (EAE), a mouse model of brain inflammation has proven very useful for the investigation of the mechanisms that may underlie the development of MS. We want to use this model to investigate the importance of molecules involved in apoptosis and inflammation in the induction of disease. We will employ conditional gene targeting to study the involvement of two genes, which have been shown to play a major role in brain inflammation: fas and gp130, a receptor essential for response to the cytokine IL-6. Fas deficient mice were shown to be resistant to EAE induction. To test in which cell types expression of Fas contributes to brain inflammation, we will use mice in which the fas gene can be deleted in a tissue-specific manner. Similarly, because IL-6 deficient mice were shown to be resistant to EAE induction, we will use conditional gene deletion of a receptor essential for IL-6 response, gp130, to test which brain cells are important in the response to this pro-inflammatory cytokine. We use brain cell-specific Cre mice to delete the fas or the gp130 genes in oligodendrocytes, astrocytes or whole brain. The information obtained from theses experiments will shed light on molecules and cells involved in MS induction and development and allow us to design new strategies to combat this disease.

• DFG Programme: Research Grants