The sphingosine-1-phosphate transporter Spns2 expressed on endothelial cells regulates lymphocyte trafficking in mice
The sphingosine-1-phosphate transporter Spns2 expressed on endothelial cells regulates lymphocyte trafficking in mice
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DOI：
10.1172/jci60746
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发表时间：
2012-04-01
影响因子：
15.9
通讯作者：
Mochizuki, Naoki
中科院分区：
文献类型：
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作者：
Fukuhara, Shigetomo;Simmons, Szandor;Mochizuki, Naoki
生物活性溶血磷脂介体鞘氨醇-l-磷酸（SIP）促进新形成的T细胞从胸腺中排出和未成熟的B细胞从骨髓中释放。然而，目前还不清楚SIP在哪里以及如何发布。在这里，我们表明，在小鼠中，SIP转运蛋白spinster同系物2（Spns 2）是负责出口的成熟T细胞和未成熟的B细胞从胸腺和骨髓，分别。Global Spns 2-KO小鼠表现出胸腺中成熟T细胞的显著积累，血液和次级淋巴器官中外周T细胞数量减少。成熟再循环B细胞在骨髓以及血液和次级淋巴器官中的频率降低。骨髓重建研究表明，Spns 2不参与SW从血细胞的释放，并建议在其他细胞中的Spns 2的作用。与这些数据一致，Spns 2的内皮特异性缺失导致淋巴细胞流出缺陷，与在整体Spns 2-KO小鼠中观察到的缺陷相似。这些数据表明，Spns 2在EC中的功能是建立T和B细胞从其各自的初级淋巴器官中排出所需的S1 P梯度。此外，Spns 2可能是一系列炎症和自身免疫性疾病的治疗靶点。
The bioactive lysophospholipid mediator sphingosine-l-phosphate (SIP) promotes the egress of newly formed T cells from the thymus and the release of immature B cells from the bone marrow. It has remained unclear, however, where and how SIP is released. Here, we show that in mice, the SIP transporter spinster homolog 2 (Spns2) is responsible for the egress of mature T cells and immature B cells from the thymus and bone marrow, respectively. Global Spns2-KO mice exhibited marked accumulation of mature T cells in thymi and decreased numbers of peripheral T cells in blood and secondary lymphoid organs. Mature recirculating B cells were reduced in frequency in the bone marrow as well as in blood and secondary lymphoid organs. Bone marrow reconstitution studies revealed that Spns2 was not involved in SW release from blood cells and suggested a role for Spns2 in other cells. Consistent with these data, endothelia-specific deletion of Spns2 resulted in defects of lymphocyte egress similar to those observed in the global Spns2-KO mice. These data suggest that Spns2 functions in ECs to establish the S1P gradient required for T and B cells to egress from their respective primary lymphoid organs. Furthermore, Spns2 could be a therapeutic target for a broad array of inflammatory and autoimmune diseases.