Importantly, pathology further correlated with decreases in both Tregs and IL-10, but not with increased antigen specific Th17 cells, although astrocytes are critical targets of IL-17 [41] . Although it is possible that the increased IFN-c in the CNS influenced peripheral activation of antigen specific Th17 cells, previous data demonstrated no evidence for expression of the transgene in peripheral organs, including lymphoid organs [18] . IL-10, secreted by a variety of cells types including CD4 + T cells, CD8 + T cells and Tregs [42] , inhibits both acute and chronic EAE [43, 44] . The decrease in this anti-inflammatory cytokine suggests that the induction of IL-27 secretion is a critical aspect of astrocyte responses to IFN-c, thus promoting IL-10 secretion by T cells [23, 25] . However, our data is unable to distinguish the contribution of paracrine versus autocrine IFN-c induced signals to astrocytes on IL-10 production, as IL-10 also regulates astrocyte activation [22] , and can itself be secreted by astrocytes to exert autologous functions [45] .