טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
Ph.D Thesis
Ph.D StudentNetzer Nir
SubjectThe Role of Scavenger Receptor Class B (SR-BI) in the
Development of T Cell Mediated Autoimmune
Diseases
DepartmentDepartment of Biotechnology
Supervisor Professor Nathan Karin


Abstract

In my study we have used a unique platform that we have developed to define naturally produced antibodies that bind a cell surface molecule of inflammatory macrophages.  These antibodies bind cell surface molecule that is traditionally affiliated with the metabolism of high-density lipoproteins (HDL). The production of these antibodies is elicited during autoimmune diseases and regulated by the severity of the disease. We have amplified this response using a DNA vaccine based technology and then studied their biological properties. It appears that these antibodies redirect the cytokine production of target macrophages. They suppress the production of pro inflammatory mediators like TNF-a and IL-12 and at the same time enhance the production of the anti-inflammatory mediator IL-10. It appears that HDL can, less effectively generate the same effect. Therefore we think that during the evolution this system has evolved as a natural mechanism to restrain the pathogenic consequences of the immune system. We have then tried to explore the therapeutic potential of these antibodies. Their administration to rats and mice suffering from inflammatory autoimmune disease, like experimentally induced multiple sclerosis, suppress these diseases. We hope to extend these interesting findings to patients suffering from these diseases in the future.  We have also used the novel system that we have established to follow the intracellular events leading to altered cytokine production by these macrophages. This interesting study is now being intensively explored in our laboratory.