טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
Ph.D Thesis
Ph.D StudentMeiron Moran
SubjectDual Function of SDF-1 in the Regulation of Experimental
Autoimmune Encephalomyelitis
DepartmentDepartment of Medicine
Supervisor Professor Nathan Karin


Abstract

Stromal Cell Derived Factor-1 (SDF-1) is a chemokine which is expressed constitutively by various cell types, and thought to direct different biological functions. In the current study we have used the DNA vaccination technology to breakdown the tolerance to this protein and generated autoantibody response against it. The adoptive transfer of these neutralizing antibodies during ongoing Experimental Autoimmune Encephalomyelitis (EAE) aggravated, rather than suppressed, its clinical manifestation. Subsequently we have shown that SDF-1 displays a regulatory role in this, and possibly in other, T cell mediated autoimmune diseases by directing the function of invading macrophages from pro inflammatory to IL-10 production anti inflammatory macrophages.  Finally, we have constructed a human SDF-1-Ig fusion protein and demonstrate its competence to suppress an ongoing disease in mice. These results suggest a regulatory effect of SDF-1 and led us to the conclusion that SDF-1 might have a dual function in the regulation of EAE. On one hand, it directs T cells and macrophages to sites of inflammation, thus promoting the inflammatory process, while on the other hand, it shifts the cytokine balance of activated macrophages, and perhaps T cells, toward a regulatory phenotype. This study than not only demonstrate, for the first time, the pivotal role of a chemokine as a regulatory mediator, but also suggested a novel way for therapy of EAE and possibly other T cells mediated autoimmune diseases.