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Finding a Way Out: S1P Signaling and Immune Cell Migration
Annual Review of Immunology ( IF 26.9 ) Pub Date : 2020-04-27
Audrey A.L. Baeyens, Susan R. Schwab

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:


寻找出路:S1P信号传导和免疫细胞迁移

信号脂质神经鞘氨醇1-磷酸(S1P)在免疫反应中起关键作用。靶向S1P信号转导的药物在治疗多发性硬化症方面已经非常成功,并且在结肠炎和牛皮癣的临床试验中显示出了希望。这些药物的一种机制是阻止淋巴细胞从最初激活淋巴细胞的淋巴结进入循环,从而使淋巴细胞可以到达炎症部位。确实,S1P可以被认为是一种循环标志物,可以向免疫细胞发出信号以帮助他们找到血液和淋巴管,并向内皮细胞发出信号以稳定脉管系统。就是说,S1P在免疫反应中发挥多效性的作用,建立有关S1P如何形成炎症的综合观点非常重要。S1P可以如此有效地起作用,因为它的分布受到严格控制。在这里,我们将回顾S1P梯度如何调节免疫细胞从组织中排出,并特别关注该领域中的关键悬而未决的问题。

更新日期:2020-04-27
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