Sphingosine-1-Phosphate Signaling in Immune Cells and Inflammation: Roles and Therapeutic Potential.
Sphingosine-1-Phosphate Signaling in Immune Cells and Inflammation: Roles and Therapeutic Potential.
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DOI：
10.1155/2016/8606878
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发表时间：
2016
影响因子：
4.6
通讯作者：
Takabe K
中科院分区：
文献类型：
--
作者：
Aoki M;Aoki H;Ramanathan R;Hait NC;Takabe K
1-磷酸鞘氨醇（S1 P）是一种生物活性鞘脂代谢产物，参与许多关键细胞过程。它是由鞘氨醇激酶（SphKs）磷酸化鞘氨醇产生的，并通过转运蛋白如spinster同系物2（Spns 2）输出细胞。S1 P通过与特异性G蛋白结合受体S1 P受体（S1 PRs）1-5结合，通过一个被称为“由内而外的信号传导”的过程来调节多种生理过程。不同组织之间的S1 P浓度梯度促进T细胞从次级淋巴器官向淋巴和血液循环的S1 PR 1依赖性迁移。S1 P抑制T细胞从发炎的外周组织中流出并促进其在发炎的外周组织中的滞留。T和B细胞中的S1 PR 1以及内皮细胞中的Spns 2有助于淋巴细胞运输。FTY 720（芬戈莫德）是S1 PR的功能性拮抗剂，其通过抑制淋巴细胞从淋巴器官排出而诱导全身性淋巴细胞减少症。在这篇综述中，我们总结了以前的研究结果和新发现的重要性，S1 P和S1 PR信号在招募免疫细胞和淋巴细胞保留在发炎组织。我们还讨论了S1 P-S1 PR 1轴在炎症性疾病和创伤愈合中的作用。
Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid metabolite involved in many critical cell processes. It is produced by the phosphorylation of sphingosine by sphingosine kinases (SphKs) and exported out of cells via transporters such as spinster homolog 2 (Spns2). S1P regulates diverse physiological processes by binding to specific G protein-binding receptors, S1P receptors (S1PRs) 1–5, through a process coined as “inside-out signaling.” The S1P concentration gradient between various tissues promotes S1PR1-dependent migration of T cells from secondary lymphoid organs into the lymphatic and blood circulation. S1P suppresses T cell egress from and promotes retention in inflamed peripheral tissues. S1PR1 in T and B cells as well as Spns2 in endothelial cells contributes to lymphocyte trafficking. FTY720 (Fingolimod) is a functional antagonist of S1PRs that induces systemic lymphopenia by suppression of lymphocyte egress from lymphoid organs. In this review, we summarize previous findings and new discoveries about the importance of S1P and S1PR signaling in the recruitment of immune cells and lymphocyte retention in inflamed tissues. We also discuss the role of S1P-S1PR1 axis in inflammatory diseases and wound healing.