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Biochemical Pharmacology
Li, Z;Chen, X;Chen, Y;Li, H;Yu, J;Li, Y;Zhu, W;Xie, Y;Tian, Y;Su, W;Liang, D;
Autoimmune uveitis (AU), a sight-threatening intraocular disorder, is still a challenge for ophthalmologists in clinic. Teriflunomide has been approved for multiple sclerosis (MS) in 2012 for its immunoregulatory function. However, the effect and mechanisms of teriflunomide in uveitis are still unknown. In this investigation, we used a murine model of non-infectious uveitis, experimental autoimmune uveitis (EAU), to explore the anti-inflammatory features of teriflunomide. Treatment with teriflunomide resulted in reduced clinical and pathological scores of retinal inflammation, accompanied by decreased intraocular infiltration of Th17 and Th1 cells in EAU mice. Meanwhile, teriflunomide treatment inhibited the proliferation and polarization of CD4+ T cells to Th17 and Th1 cells. Moreover, adoptive transfer of teriflunomide primed IRBP1-20-T cells failed to induce EAU. Interestingly, we found that teriflunomide suppressed the maturation and function of dendritic cells (DCs) both in vivo and in vitro. In conclusion, our findings suggest that teriflunomide alleviates inflammation in EAU mice by down-regulating Th17 and Th1 cells and suppresses the maturation and function of DCs for the first time. Copyright 2019. Published by Elsevier Inc.