Georgetown University Washginton, District of Columbia, United States
Abstract Text: Multiple sclerosis (MS) is an autoimmune disease mediated by the infiltration of autoreactive T cells into the central nervous system (CNS) leading to chronic demyelination. Excessive demyelination leads to axonal damage and neurodegeneration. Upon demyelinating injury, myelin producing oligodendrocyte precursor cells (OPCs) are recruited to the site of damage, where they differentiate into mature oligodendrocytes and restore myelin in an endogenous process known as remyelination. Unfortunately, with disease progression, remyelination fails to occur for reasons not fully understood. One possibility for remyelination failure is unresolved inflammation in the CNS caused by the proliferation and differentiation of effector T cells in response to damage. Amino acids are essential in providing T cells with the fuel to proliferate and differentiate during an immune response. Hence, I will examine the role of the large neutral amino acid transporter, Slc7a5, in effector T-cells in mice under immune mediated demyelination. Experimental autoimmune encephalomyelitis (EAE) was induced in mice lacking Slc7a5 in CD4+ T cells (Slc7a5 f/f CD4-Cre). We found that the Slc7a5 f/f CD4-Cre mice displayed a significant decrease in EAE severity scores compared to control mice. Moreover, flow cytometry analysis of T-cell population in the spinal cord of these Slc7a5f/f CD4-Cre EAE mice revealed a significant decrease in proinflammatory T-cells. Our results suggest that T-cells utilize the Slc7a5 transporter and amino acids to initiate an inflammatory response in mouse models of MS, and that both amino acids and Slc7a5 may be potential novel immunomodulatory targets for preventing disease progression in MS.
