Grant: Operating Grant

Multiple sclerosis (MS) is a condition in which immune cells become activated and they then enter the brain and spinal cord in large numbers to produce neuronal injury. We have implicated a new molecule, EMMPRIN, in the MS disease process. In particular, we have determined that EMMPRIN becomes highly expressed in MS blood cells and brain lesions, and that EMMPRIN increases the activity of T lymphocytes and their capacity to harm neurons in culture. In this renewal application, we seek new knowledge on the role of EMMPRIN in the MS disease process. Specifically, we first will determine how EMMPRIN increases the activity of T cells, by interrogating the molecular mechanisms by which EMMPRIN dictates how T cells are activated. We will also address how EMMPRIN aids in the T cell killing of neurons, a very important step that leads to the progression of disability in MS. A second major aim will use a transgenic mouse line that we recently generated, in order to delete EMMPRIN in particular immune cell subsets at particular times during EAE, an animal model of MS. Specifically, we wish to identify exactly which immune cell subset uses EMMPRIN to promote inflammation and injury, and when during the disease. Thirdly, we will ask how EMMPRIN is expressed and regulated in immune cells that we will obtain from living MS patients. Here, we will investigate whether the elevation of EMMPRIN in particular immune cell subset predicts an impending relapse. These experiments will help in deciphering the importance of a new molecule that we have discovered in MS, and they will help in how we design new drugs to treat MS.