Regulation of astrocyte activity and T-cell pathogenicity in CNS inflammation.
MS is a chronic autoimmune disease. In most patients, MS initially presents as a relapsing-remitting clinical course that is followed by a progressive phase characterized by a continued and irreversible accumulation of disability. Current FDA approved MS therapies act by modulating or suppressing the peripheral immune response and have a limited, if any, effect on progressive forms of MS. Furthermore, many of these therapies are associated with serious side effects. Therefore, identifying novel therapies that address chronic CNS inflammation associated with the different forms of MS remains a major unmet need. EAE serves as the primary animal model for MS and has led to the development of many of the current FDA-approved therapies for MS. The role of CD4+ T cells in the pathogenesis of EAE is well established. Immunization with myelin antigen induces autopathogenic T cells that home to the CNS and induce a pro-inflammatory response that results in demyelination and clinical disease. Astrocytes are the most abundant cells in the CNS, playing a key role in brain homeostasis and neuroinflammation. In the context of MS and EAE, astrocytes regulate the infiltration of peripheral leukocytes to the CNS and regulate the activity of microglia, oligodendrocytes, and cells of the adaptive immune system. Thus, the identification of new factors that regulate astrocyte activity and T-cell pathogenicity has the potential to help the development of new therapies for MS.