Department of Biochemistry and Molecular Biology and the Massey Cancer Center, Virginia Commonwealth University School of Medicine, Richmond, Virginia 23298, USA.
Nat Rev Immunol. 2011 Jun;11(6):403-15. doi: 10.1038/nri2974. Epub 2011 May 6.
The potent lipid mediator sphingosine-1-phosphate (S1P) is produced inside cells by two closely related kinases, sphingosine kinase 1 (SPHK1) and SPHK2, and has emerged as a crucial regulator of immunity. Many of the actions of S1P in innate and adaptive immunity are mediated by its binding to five G protein-coupled receptors, designated S1PR1-5, but recent findings have also identified important roles for S1P as a second messenger during inflammation. In this Review, we discuss recent advances in our understanding of the roles of S1P receptors and describe the newly identified intracellular targets of S1P that are crucial for immune responses. Finally, we discuss the therapeutic potential of new drugs that target S1P signalling and functions.
强效脂质介质 1-磷酸鞘氨醇（S1P）由两种密切相关的激酶，即鞘氨醇激酶 1（SPHK1）和 SPHK2 在细胞内产生，现已成为免疫的关键调节剂。S1P 在先天和适应性免疫中的许多作用是通过其与五个 G 蛋白偶联受体（称为 S1PR1-5）结合来介导的，但最近的发现也表明 S1P 在炎症期间作为第二信使具有重要作用。在这篇综述中，我们讨论了我们对 S1P 受体作用的理解的最新进展，并描述了 S1P 的新鉴定的细胞内靶标，这些靶标对免疫反应至关重要。最后，我们讨论了针对 S1P 信号和功能的新药的治疗潜力。
