Nuclear factor of activated T cells (NFATs) is an important transcription factor for T cell activation and proliferation. Recent studies have highlighted the role of NFATs in regulating the differentiation of effector CD4 T helper (Th) subsets including Th1 and Th17 cells. Because controlling the effector T cell function is important for the treatment of autoimmune diseases, regulation of NFAT functions in T cells would be an important strategy to control the pathogenesis of autoimmune diseases. Here, we demonstrated that an NFAT inhibitory peptide, VIVIT conjugated to dNP2 (dNP2-VIVIT), a blood-brain barrier-permeable peptide, ameliorated experimental autoimmune encephalomyelitis (EAE) by inhibiting Th1 and Th17 cells, but not regulatory T (T_reg) cells. dNP2-VIVIT negatively regulated spinal cord-infiltrating interleukin-17A (IL-17A) and interferon (IFN)-γ-producing CD4⁺ T cells without affecting the number of Foxp3⁺ CD4⁺ T_reg cells, whereas dNP2-VEET or 11R-VIVIT could not significantly inhibit EAE. In comparison with cyclosporin A (CsA), dNP2-VIVIT selectively inhibited Th1 and Th17 differentiation, whereas CsA inhibited the differentiation of all T cell subsets including that of Th2 and T_reg cells. Collectively, this study demonstrated the role of dNP2-VIVIT as a novel agent for the treatment of autoimmune diseases such as multiple sclerosis by regulating the functions of Th1 and Th17 cells.

活化的T细胞（NFAT）的核因子是T细胞活化和增殖的重要转录因子。最近的研究强调了NFAT在调节效应CD4 T辅助（Th）亚群（包括Th1和Th17细胞）分化中的作用。由于控制效应T细胞功能对自身免疫性疾病的治疗很重要，因此调节T细胞中NFAT功能将是控制自身免疫性疾病发病机理的重要策略。在这里，我们证明了NFAT抑制肽VIVIT与血脑屏障可渗透肽dNP2（dNP2-VIVIT）偶联，通过抑制Th1和Th17细胞而不是调节性T（T _reg） 细胞。dNP2-VIVIT负调节脊髓浸润的白介素17A（IL-17A）和产生干扰素（IFN）-γ的CD4 ⁺ T细胞，而不会影响Foxp3 ⁺ CD4 ⁺ T _reg细胞的数量，而dNP2-VEET或11R- VIVIT不能显着抑制EAE。与环孢菌素A（CsA）相比，dNP2-VIVIT选择性抑制Th1和Th17分化，而CsA抑制所有T细胞亚群的分化，包括Th2和T _reg细胞。总体而言，这项研究证明了dNP2-VIVIT作为一种新型药物，可通过调节Th1和Th17细胞的功能来治疗自身免疫性疾病，如多发性硬化症。