Prolonging survival of corneal transplantation by selective sphingosine-1-phosphate receptor 1 agonist.
Prolonging survival of corneal transplantation by selective sphingosine-1-phosphate receptor 1 agonist.
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通过选择性 1-磷酸鞘氨醇受体 1 激动剂延长角膜移植的存活率。
DOI：
10.1371/journal.pone.0105693
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Huang Y
中科院分区：
文献类型：
--
作者：
Gao M;Liu Y;Xiao Y;Han G;Jia L;Wang L;Lei T;Huang Y
角膜移植是治疗眼病最常用的方法。虽然角膜在某种程度上是一个免疫特权器官，但免疫排斥仍然是降低成功率的主要问题。因此，需要有效调节免疫反应的化学药物来改善角膜移植的预后。本研究系统评估了鞘氨醇-1-磷酸受体1 （S1P1）选择性激动剂在小鼠异体角膜移植中的作用，并与常用的免疫抑制剂进行了比较。与CsA和非选择性S1P1受体激动剂FTY720相比，S1P1选择性激动剂可使角膜移植存活时间延长30天以上，且免疫应答较低。更重要的是，S1P1选择性激动剂的最佳剂量远小于非选择性S1P受体激动剂FTY720，这将降低药物应用中的剂量依赖性毒性。然后，我们分析了所选择的S1P1选择性激动剂对免疫抑制的机制。结果表明，S1P1选择性激动剂可调节同种异体移植物中CD4+ T细胞减少、Treg细胞增强的免疫细胞分布，调节抗炎细胞因子TGF-β1、IL-10的表达，减轻免疫反应。这些发现表明，S1P1选择性激动剂可能是一种更合适的免疫抑制化合物，可以有效延长小鼠异体角膜移植物的存活时间。
Corneal transplantation is the most used therapy for eye disorders. Although the cornea is somewhat an immune privileged organ, immune rejection is still the major problem that reduces the success rate. Therefore, effective chemical drugs that regulate immunoreactions are needed to improve the outcome of corneal transplantations. Here, a sphingosine-1-phosphate receptor 1 (S1P1) selective agonist was systematically evaluated in mouse allogeneic corneal transplantation and compared with the commonly used immunosuppressive agents. Compared with CsA and the non-selective sphingosine 1-phosphate (S1P) receptor agonist FTY720, the S1P1 selective agonist can prolong the survival corneal transplantation for more than 30 days with a low immune response. More importantly, the optimal dose of the S1P1 selective agonist was much less than non-selective S1P receptor agonist FTY720, which would reduce the dose-dependent toxicity in drug application. Then we analyzed the mechanisms of the selected S1P1 selective agonist on the immunosuppression. The results shown that the S1P1 selective agonist could regulate the distribution of the immune cells with less CD4+ T cells and enhanced Treg cells in the allograft, moreover the expression of anti-inflammatory cytokines TGF-β1 and IL-10 unregulated which can reduce the immunoreactions. These findings suggest that S1P1 selective agonist may be a more appropriate immunosuppressive compound to effectively prolong mouse allogeneic corneal grafts survival.
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