Teriflunomide suppresses T helper cells and dendritic cells to alleviate experimental autoimmune uveitis
Teriflunomide suppresses T helper cells and dendritic cells to alleviate experimental autoimmune uveitis
复制标题
特立氟胺抑制 T 辅助细胞和树突状细胞以缓解实验性自身免疫性葡萄膜炎
DOI：
10.1016/j.bcp.2019.113645
复制
发表时间：
2019-12-01
影响因子：
5.8
通讯作者：
Liang, Dan
中科院分区：
文献类型：
--
作者：
Li, Zhuang;Chen, Xiaoqing;Liang, Dan
自身免疫性葡萄膜炎(AU)是一种严重威胁视力的眼内疾病，临床上仍是眼科医生面临的一大难题。特氟米特因其免疫调节功能已于2012年被批准用于多发性硬化症(MS)。然而，特氟米特治疗葡萄膜炎的疗效和作用机制尚不清楚。在这项研究中，我们使用了一种非感染性葡萄膜炎的小鼠模型，实验性自身免疫性葡萄膜炎(EAU)，以探讨特氟米特的抗炎特性。特氟米特治疗导致EAU小鼠视网膜炎症的临床和病理评分降低，同时眼内Th17和Th1细胞浸润减少。同时，特氟米特抑制了CD4+T细胞对Th17和Th1细胞的增殖和极化。过继转移特氟米特诱导的IRBP1-20-T细胞不能诱导EAU。有趣的是，我们发现特氟米特在体内和体外都抑制树突状细胞(DC)的成熟和功能。综上所述，我们的研究结果表明，特氟米特通过下调Th17和Th1细胞来减轻EAU小鼠的炎症反应，并首次抑制DC的成熟和功能。
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 inflammations, 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.