Sphingosine-1-phosphate receptor 1 agonist SEW2871 prolongs heterotopic heart allograft survival in mice
Sphingosine-1-phosphate receptor 1 agonist SEW2871 prolongs heterotopic heart allograft survival in mice
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DOI：
10.1016/j.intimp.2015.03.004
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发表时间：
2015-05-01
影响因子：
5.6
通讯作者：
Yin, Hui
中科院分区：
文献类型：
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作者：
Ni, Qian;Yuan, Baohong;Yin, Hui
鞘氨醇-l-磷酸（SIP）是质膜鞘脂的生物活性代谢物，其对于免疫细胞运输是必需的。最近的研究表明，SIP及其受体（S1PR1-S1PR5）在许多炎症性疾病中具有免疫调节功能，如哮喘和自身免疫。在这里，我们探讨SEW2871，一种选择性S1PR1激动剂，在小鼠心脏移植模型中预防急性同种异体排斥反应的疗效。与用对照媒介物处理的那些受体相比，用SEW2871处理受体小鼠显著降低心脏同种异体移植物存活。移植物存活率的提高与循环淋巴细胞减少和同种异体移植物炎性细胞浸润有关。细胞因子分析显示，SEW 2871处理的小鼠中TNF-alpha、IFN-gamma和IL-2的同种异体移植物表达减少。此外，SEW2871的施用增加了同种异体移植物受体脾脏中的CD4（+）T调节细胞的百分比和FoxP3表达。因此，SEW2871在调节淋巴细胞运输和发育中起关键作用，这直接有助于延长同种异体移植物存活。(C)2015爱思唯尔B.V.保留所有权利。
Sphingosine-l-phosphate (SIP) is a biologically active metabolite of plasma-membrane sphingolipids that is essential for immune cell trafficking. Recent studies have revealed immunomodulatory functions of SIP and its receptors (S1PR1-S1PR5) in many inflammatory conditions, such as asthma and autoimmunity. Here, we explore the efficacy of SEW2871, a selective S1PR1 agonist, in the prevention of acute allograft rejection in a murine cardiac transplantation model. Treatment of recipient mice with SEW2871 significantly prolongs cardiac allograft survival as compared to those recipients treated with control vehicle. The enhanced graft survival is associated with reduced circulating lymphocytes and allograft inflammatory cell infiltration. The cytokine analysis showed decreased allograft expression of TNF-alpha, IFN-gamma and IL-2 in the SEW2871-treated mice. Moreover, administration of SEW2871 increases the percentage of CD4(+) T regulatory cells and FoxP3 expression in spleen of allograft recipients. Therefore, SEW2871 plays a critical role in regulation of lymphocyte trafficking and development, which directly contributes to prolongation of the allograft survival. (C) 2015 Elsevier B.V. All rights reserved.