Lipid phosphate phosphatase 3 enables efficient thymic egress.
Lipid phosphate phosphatase 3 enables efficient thymic egress.
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DOI：
10.1084/jem.20102551
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发表时间：
2011-06-06
期刊：
影响因子：
--
通讯作者：
Schwab SR
中科院分区：
文献类型：
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作者：
Bréart B;Ramos-Perez WD;Mendoza A;Salous AK;Gobert M;Huang Y;Adams RH;Lafaille JJ;Escalante-Alcalde D;Morris AJ;Schwab SR
内皮细胞和上皮细胞中的脂质磷酸盐磷酸酶3促进T细胞从胸腺向外周的有效迁移。信号脂质鞘鞘醇-1-磷酸（S1P）稳定脉管系统，指导淋巴细胞从淋巴器官流出，并形成炎症反应。然而，关于体内如何控制S1P分布知之甚少，并且不清楚无处不在的脂质如何作为需要精确的空间和时间控制的信号发挥作用。我们发现脂质磷酸盐磷酸酶3 （LPP3）能够有效地将成熟T细胞从胸腺出口到循环中，并且有几条证据表明LPP3通过破坏胸腺S1P促进出口。尽管胸腺中表达了另外五种磷酸降解酶，但它们不能弥补LPP3的损失。此外，上皮细胞或内皮细胞中LPP3的条件缺失足以抑制其分泌。这些结果表明S1P的产生和破坏受到严格的调控，LPP3对建立平衡至关重要。
Lipid phosphate phosphatase 3 in endothelial and epithelial cells promotes efficient T cell emigration from the thymus to the periphery. The signaling lipid sphingosine-1-phosphate (S1P) stabilizes the vasculature, directs lymphocyte egress from lymphoid organs, and shapes inflammatory responses. However, little is known about how S1P distribution is controlled in vivo, and it is not clear how a ubiquitously made lipid functions as a signal that requires precise spatial and temporal control. We have found that lipid phosphate phosphatase 3 (LPP3) enables efficient export of mature T cells from the thymus into circulation, and several lines of evidence suggest that LPP3 promotes exit by destroying thymic S1P. Although five additional S1P-degrading enzymes are expressed in the thymus, they cannot compensate for the loss of LPP3. Moreover, conditional deletion of LPP3 in either epithelial cells or endothelial cells is sufficient to inhibit egress. These results suggest that S1P generation and destruction are tightly regulated and that LPP3 is essential to establish the balance.