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Introduction We and others recently showed that IL-17-producing Th17 cells are highly unstable in their phenotype and swiftly upregulate T-bet and Th1-associated cytokines in the inflamed CNS of mice with EAE [1] . This inherent plasticity was recently associated with IL-23, IFN-γ or IL-12 signalling on effector T cells [2] , [3] . Aim To understand the role of IFN-γ and IL-27 signaling for plasticity of Th17 cells in vivo. Methods We use mice lacking the IFN-γ receptor 2 chain specifically in T cells (CD4cre × IFNγR2FL/FL) as well as blocking antibodies for IFN-γ and IL-27-p28 and knockout mice for IL-27-EBI3. Further we use IL-17 reporter mice to sort Th17 cells prior adoptive transfer. We use experimental autoimmune encephalomyelitis (EAE) as in vivo CNS inflammation model in which Th17 cells play an important role and in which plasticity of Th17 cells is predominant found in the CNS. Results Using CD4cre × IFNγR2FL/FL mice we found that IFN-g signaling on T cells has a suppressive role in transfer EAE but it is negligible for Th17 plasticity in vivo. We therefore screened several cytokines in vitro and found that IL-27 signaling has a strong impact on Th17 plasticity. In vitroTh17 cells shifted strongly to Th1 when restimulated with IL-12 and IL-27 even in absence of IFN-γ signaling. To investigate the in vivo effects of IL-28 and IFN-γ on Th17 plasticity, experiments are currently performed in CD4cre × IFNγR2FL/FL mice in combination with an IL-27-p28 neutralizing monoclonal antibody or the complete IL-27-EBI3 knockout model. Conclusion Although IFN-γ signaling on T cells has a suppressive role in transfer EAE it does not by itself influence Th17 plasticity in the CNS. We suggest that it may act in a redundant fashion with other cytokines such as IL-27 to induce the Th1 shift of Th17 cells under inflammatory conditions.