Limiting inflammation following either infection or during an autoimmune attack is a prerequisite for the initiation of repair. This is critically important within the CNS which has limited regenerative capacity. In summary, our data identify astrocytes as prominent targets underlying IFN-c mediated suppression of chronic CNS inflammation [19] . The data further provide a link between sustained inflammatory responses, enhanced demyelination and axonal degeneration associated with loss of neurological function during EAE and chronic progressive MS. Although the inability of astrocytes to respond to IFN-c did not alter disease in the brain, engagement of the IFN-c receptor on astrocytes in spinal cord limits demyelination and functions in a neuroprotective capacity. Current therapies for MS are primarily focused on antiinflammatory and immunomodulatory approaches and have been partially successful in treating acute episodes. The identification of astrocytes as critical responders and mediators of IFN-c signaling in limiting CNS autoimmune disease may provide insights into new approaches to limit long term progression to disability. 