Department of Biochemistry, All India Institute of Medical Sciences (AIIMS) Bhopal, Madhya Pradesh 462020, India.
Children's Hospital Oakland Research Institute and UCSF Benioff Children's Hospital Oakland, 5700 Martin Luther King Jr. Way, Oakland, CA 94609, USA.
Mediators Inflamm. 2017;2017:7685142. doi: 10.1155/2017/7685142. Epub 2017 Dec 3.
Sphingosine-1-phosphate (S1P) is a potent lipid signaling molecule that regulates pleiotropic biological functions including cell migration, survival, angiogenesis, immune cell trafficking, inflammation, and carcinogenesis. It acts as a ligand for a family of cell surface receptors. S1P concentrations are high in blood and lymph but low in tissues, especially the thymus and lymphoid organs. S1P chemotactic gradients are essential for lymphocyte egress and other aspects of physiological cell trafficking. S1P is irreversibly degraded by S1P lyase (SPL). SPL regulates lymphocyte trafficking, inflammation and other physiological and pathological processes. For example, SPL located in thymic dendritic cells acts as a metabolic gatekeeper that controls the normal egress of mature T lymphocytes from the thymus into the circulation, whereas SPL deficiency in gut epithelial cells promotes colitis and colitis-associated carcinogenesis (CAC). Recently, we identified a complex syndrome comprised of nephrosis, adrenal insufficiency, and immunological defects caused by inherited mutations in human , the gene encoding SPL. In the present article, we review current evidence supporting the role of SPL in thymic egress, inflammation, and cancer. Lastly, we summarize recent progress in understanding other SPL functions, its role in inherited disease, and SPL targeting for therapeutic purposes.
鞘氨醇-1-磷酸（S1P）是一种有效的脂质信号分子，调节多种生物功能，包括细胞迁移、存活、血管生成、免疫细胞迁移、炎症和癌症发生。它作为细胞表面受体家族的配体发挥作用。S1P 浓度在血液和淋巴中较高，但在组织中较低，特别是在胸腺和淋巴器官中。S1P 趋化梯度对于淋巴细胞渗出和其他生理细胞迁移方面至关重要。S1P 被 S1P 裂解酶（SPL）不可逆地降解。SPL 调节淋巴细胞迁移、炎症和其他生理和病理过程。例如，位于胸腺树突状细胞中的 SPL 作为代谢守门员，控制成熟 T 淋巴细胞从胸腺正常流出到循环中，而肠道上皮细胞中的 SPL 缺乏会促进结肠炎和结肠炎相关的癌症发生（CAC）。最近，我们鉴定了一种由人类 SPL 基因编码的 SPL 遗传突变引起的肾病、肾上腺功能不全和免疫缺陷的复杂综合征。在本文中，我们综述了支持 SPL 在胸腺迁出、炎症和癌症中的作用的现有证据。最后，我们总结了对 SPL 其他功能、其在遗传性疾病中的作用以及 SPL 靶向治疗目的的最新认识。
