S1P Lyase Regulation of Thymic Egress and Oncogenic Inflammatory Signaling.
S1P Lyase Regulation of Thymic Egress and Oncogenic Inflammatory Signaling.
复制标题
DOI：
10.1155/2017/7685142
复制
发表时间：
2017
影响因子：
4.6
通讯作者：
Saba JD
中科院分区：
文献类型：
--
作者：
Kumar A;Zamora-Pineda J;Degagné E;Saba JD
鞘氨醇-1-磷酸（S1 P）是一种有效的脂质信号分子，其调节多效性生物学功能，包括细胞迁移、存活、血管生成、免疫细胞运输、炎症和致癌。它作为一个细胞表面受体家族的配体。血液和淋巴中的S1 P浓度较高，但组织中的浓度较低，尤其是胸腺和淋巴器官。S1 P趋化性梯度对于淋巴细胞流出和生理细胞运输的其他方面是必不可少的。S1 P被S1 P裂解酶（SPL）不可逆地降解。SPL调节淋巴细胞运输，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充当代谢看门人，其控制成熟T淋巴细胞从胸腺正常流出到循环中，而肠上皮细胞中的SPL缺乏促进结肠炎和结肠炎相关的致癌作用（CAC）。最近，我们发现了一种复杂的综合征，包括肾病，肾上腺功能不全，和免疫缺陷所造成的遗传突变的人SGPL 1，编码SPL的基因。在这篇文章中，我们回顾了目前支持SPL在胸腺出口、炎症和癌症中作用的证据。最后，我们总结了最近的进展，了解其他SPL功能，其在遗传性疾病中的作用，SPL靶向治疗的目的。
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 SGPL1, 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.