S1P1 receptor expression regulates emergence of NKT cells in peripheral tissues
S1P1 receptor expression regulates emergence of NKT cells in peripheral tissues
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DOI：
10.1096/fj.07-9087com
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发表时间：
2008-01-01
期刊：
影响因子：
4.8
通讯作者：
Proia, Richard L.
中科院分区：
文献类型：
--
作者：
Allende, Maria L.;Zhou, Dapeng;Proia, Richard L.
淋巴细胞和内皮细胞表面的S1 P（1）受体调节某些淋巴细胞群体的独特运输行为。我们已经研究了S1 P（1）受体是否也决定了V α 14-J α 18自然杀伤T（NKT）细胞的独特组织分布，其运输模式尚不清楚。小鼠（TCS 1 P（1）KO）在胸腺细胞（包括NKT细胞前体）中条件性缺失S1 P（1）受体。在胸腺内，发现NKT细胞处于正常或增加的水平，表明S1 P（1）受体表达与NKT细胞发育无关。然而，在TCS 1 P（1）KO小鼠的外周组织中检测到NKT细胞数量显著减少。在NKT细胞在外周建立驻留后，短期S1 P（1）缺失并没有显著改变其在组织中的分布，除了脾脏中的部分减少。FTY 720是一种S1 P（1）受体配体，对常规T细胞的运输具有强效作用，但并没有改变野生型小鼠外周组织中NKT细胞的预先存在的分布。我们的研究结果表明，S1 P（1）受体在NKT细胞上的表达对胸腺内的发育是不利的，但对它们在外周的组织驻留的建立是必不可少的。
The S1P(1) receptor, on the surface of lymphocytes and endothelial cells, regulates the unique trafficking behavior of certain lymphocyte populations. We have examined whether the S1P(1) receptor also dictates the distinctive tissue distribution of V alpha 14-J alpha 18 natural killer T (NKT) cells, whose trafficking pattern is not well understood. Mice (TCS1P(1)KO) were established with a conditional deletion of the S1P(1) receptor in thymocytes that included precursors of NKT cells. Within the thymus, NKT cells were found at normal or increased levels, indicating that S1P(1) receptor expression was dispensable for NKT cell development. However, substantially reduced numbers of NKT cells were detected in the peripheral tissues of the TCS1P(1)KO mice. Short-term S1P(1) deletion after NKT cells had established residence in the periphery did not substantially alter their distribution in tissues, except for a partial decrease in the spleen. FTY720, a S1P(1) receptor ligand that has potent effects on the trafficking of conventional T cells, did not alter the preexisting distribution of NKT cells within peripheral tissues of wild-type mice. Our results indicate that the S1P(1) receptor expression on NKT cells is dispensable for development within thymus but is essential for the establishment of their tissue residency in the periphery.