In the EAE model of MS, IFN-c functions as a proinflammatory cytokine in the early stages of disease [10, 11, 26 ], yet it also assumes a prominent anti-inflammatory role during the transition to remission [10, [12] [13] [14] [15] . Protection has been attributed to a variety of potentially interrelated mechanisms including limiting neutrophil accumulation, Th17 cell activation, IL-1R signaling, matrix metalloproteinase secretion, pro-inflammatory cytokine secretion and chemokine activity; in addition IFN-c facilitates T cell apoptosis and protects oligodendrocytes from death via an ER stress response [10, 11, 17] . The activities of astrocytes during autoimmunity also range from pro-to antiinflammatory [3] [4] [5] . However, to what extent a direct action of IFN-c on astrocytes contributes to inhibitory mechanism is unclear. The data herein demonstrate that among the multiple Early functions of astrocytes imposed by innate responses are largely pro-inflammatory during EAE [3, 6, 7, 26] . For example, astrocytes contribute to the loss of BBB integrity via secretion of reactive oxygen species, chemokines and pro-inflammatory cytokines [3] [4] [5] . This pro-inflammatory milieu is associated with initial axonal damage prior to accumulation of self reactive T cells [27] , which further promotes immune mediated damage. Blocking the pro-inflammatory transcription factor NF-kB in astrocytes improves recovery during chronic EAE [28, 29] . Supporting an initial pro-inflammatory role of astrocytes dependent on innate, not IFN-c responsiveness, inhibition of IFN-c signaling to astrocytes did not influence EAE onset or incidence, initial disease progression, astrocyte activation, or BBB integrity as indicated by similar entry of inflammatory cells into the brain. By contrast, an inflammation dampening effect of IFN-c became evident during the onset of disease remission. Astrocytes limit ongoing inflammation and pathogenic processes at several levels. They not only facilitate repair by inhibiting inflammatory cell entry into the CNS parenchyma [6, 7, 30] , but also down regulate T cell effector function and proliferation [4, 5, 21] . For example, EAE in GFAP deficient mice results in more severe and widespread inflammation [31] . In addition, T cell-astrocyte interactions as well as astrocyte secretion of an unidentified soluble product, distinct from nitric oxide, prostaglandins, or tryptophan metabolism, suppress T cell proliferation [4, 5] . T cell proliferation was also not inhibited via defective IL-2 release, despite the suggestion that T cell-astrocyte interactions facilitate secretion of anti-inflammatory cytokines [4, 5] . Lastly, astrocytes may limit inflammation by triggering apoptosis in T cells [32] . Nevertheless, the role of IFN-c signaling in these potentially anti-inflammatory, protective mechanisms is not clear.