Department of Chemical Physiology, The Scripps Research Institute, 10550 North Torrey Pines Rd, La Jolla, CA, 92037, USA,
Curr Top Microbiol Immunol. 2014;378:1-21. doi: 10.1007/978-3-319-05879-5_1.
The understanding of the role of the sphingosine 1-phosphate signaling system in immunology and host defense has deepened exponentially over the past 12 years since the discovery that lymphocyte egress was reversibly modulated by sphingosine 1-phosphate receptors, and with the development of fingolimod, a prodrug of a nonselective S1P receptor agonist, for therapeutic use in the treatment of relapsing, remitting multiple sclerosis. Innovative genetic and chemical approaches, together with structural biology, now provide a more detailed molecular understanding of a regulated lysophospholipid ligand with a variety of autocrine, paracrine, and systemic effects in physiology and pathology, based upon selective interactions with a high affinity and selective evolutionary cluster of G-protein-coupled receptors.
自发现淋巴细胞迁出可被鞘氨醇 1-磷酸受体可逆调节以来，过去 12 年中，人们对鞘氨醇 1-磷酸信号系统在免疫学和宿主防御中的作用的理解呈指数级加深，同时，非选择性 S1P 受体激动剂 fingolimod 的前药也被开发出来，用于治疗复发性、缓解性多发性硬化症。创新性的遗传和化学方法，以及结构生物学，现在为一种受调控的溶血磷脂配体提供了更详细的分子理解，这种配体在生理和病理过程中具有多种自分泌、旁分泌和全身性作用，其基础是与高亲和力和选择性进化簇的 G 蛋白偶联受体的选择性相互作用。
