IL1R KO mice have impaired Th17 cells and are protected from EAE [78] , and IL1β increases the susceptibility to and progression of relapse onset in MS [79] , implying a role for IL1β in the development of EAE and MS. EAE was abolished by a virus-expressing IL4 but not by a virus-expressing IL10 in chronic relapsing EAE. Therefore, the cytokine environment was converted from a disease-promoting IL23producing condition to a disease-limiting IL4-producing condition by the local expression of IL4 from a Herpes simplex virus vector delivered to the brain [80] . Moreover, the increased expression of IL4 in glial cells was associated with the reduced severity of EAE [81] , suggesting that the upregulation of Th2 cytokines inhibits the propagation of the inflammation of EAE/MS by encephalitogenic Th17 cells. CD4 + CD25 + Foxp3 + T cells, well-known regulatory T cells (Tregs), retain the potential to inhibit the autoimmune response, and protect against inflammatory injury. TGFβ is a key cytokine in the generation of Tregs. Tregs are not only primarily involved in the regulation of Th17 cells but can also regulate the functions of Th1/Th2 cells [82] . A distinction has been drawn between the generation of pathogenic Th17 cells that induce autoimmunity and the generation of Tregs that inhibit autoimmune tissue injury [39] . Although EAE was once considered a classical Th1 disease, it has been proposed that it is predominantly Th17 driven. Recently, Singh et al. demonstrated that the overexpression of IL17 in T cells did not exacerbate EAE. Moreover, genetic and antibody studies have indicated that the absence of IL17A or IL17F does not reduce the incidence or severity of EAE. The collective findings of IL17 and IFNγ studies indicate that their roles may depend on the nature of the immune response and that the IL17 that occurs in the brain may overcome the inhibitory effect of IFNγ, which generally prevents inflammation at that site [83] . When pure Th17 cells from myelin oligodendrocyte glycoprotein-(MOG-) immunized mice, polarized with TGFβ to deplete any IFNγ production, are adoptively transferred to mice, they do not induce EAE, suggesting that the reciprocal interactions among Th17-related cytokines enrol and activate the involvement of associated immune cells. Interestingly, when Th17 cells are combined with Th1 cells, they can fully induce EAE disease [84] . Liu et al. also demonstrated that the loss of STAT3 by Th cells results in an intrinsic developmental defect that renders STAT3 −/− mice resistant to CNS inflammatory diseases. STAT3 is required for the production of IL17 by Th17 cells, the generation of double positive T cells expressing IL17 and IFNγ, and T cell trafficking into CNS tissues. This suggests that STAT3 may be a therapeutic target for modulating CNS autoimmune diseases, and that Th1 cells can facilitate the entrance of Th17 cells into the CNS during EAE [85] .