The signaling lipid sphingosine 1-phosphate (S1P) plays critical roles in an immune response. Drugs targeting S1P signaling have been remarkably successful in treatment of multiple sclerosis, and they have shown promise in clinical trials for colitis and psoriasis. One mechanism of these drugs is to block lymphocyte exit from lymph nodes, where lymphocytes are initially activated, into circulation, from which lymphocytes can reach sites of inflammation. Indeed, S1P can be considered a circulation marker, signaling to immune cells to help them find blood and lymphatic vessels, and to endothelial cells to stabilize the vasculature. That said, S1P plays pleiotropic roles in the immune response, and it will be important to build an integrated view of how S1P shapes inflammation. S1P can function so effectively because its distribution is exquisitely tightly controlled. Here we review how S1P gradients regulate immune cell exit from tissues, with particular attention to key outstanding questions in the field.

中文翻译：

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寻找出路：S1P 信号传导和免疫细胞迁移。

信号脂质 1-磷酸鞘氨醇 (S1P) 在免疫反应中起着关键作用。靶向 S1P 信号传导的药物在治疗多发性硬化症方面取得了显着的成功，并且它们在结肠炎和银屑病的临床试验中显示出前景。这些药物的一种机制是阻止淋巴细胞从最初被激活的淋巴结中流出，进入循环，淋巴细胞可以从那里到达炎症部位。事实上，S1P 可以被认为是一种循环标志物，向免疫细胞发出信号以帮助它们找到血管和淋巴管，并向内皮细胞发出信号以稳定脉管系统。也就是说，S1P 在免疫反应中发挥着多效作用，建立一个关于 S1P 如何塑造炎症的综合观点非常重要。S1P 之所以能够如此有效地运作，是因为它的分布受到了极其严格的控制。在这里，我们回顾了 S1P 梯度如何调节免疫细胞从组织中退出，特别关注该领域的关键突出问题。