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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Rapid induction of medullary thymocyte phenotypic maturation and egress inhibition by nanomolar sphingosine 1-phosphate receptor agonist
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Rapid induction of medullary thymocyte phenotypic maturation and egress inhibition by nanomolar sphingosine 1-phosphate receptor agonist

机译：纳摩尔鞘氨醇1-磷酸受体激动剂可快速诱导髓样胸腺细胞表型成熟和出口抑制

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Only a small number of T cells generated in the thymus each day are selected to replenish the peripheral T cell pool. Much is known about thymic selection; however, little is known of the mechanisms regulating medullary maturation and the release of mature T cells into the blood. Here we demonstrate a rapid acceleration of medullary thymocyte phenotypic maturation through loss of CD69 induced by sphingosine 1-phosphate (S1P) receptor agonist. Low nanomolar agonist concentrations selectively induce changes in CD69(int) CD62L(high) single positive T cells, resulting in down-modulation of CD69 within 2 h. While CD69 loss is accelerated, egress of mature T cells into blood is inhibited >95% within 2 h. Both processes exhibit parallel sensitivities and dose-responses. Together, these data reveal a potent means for rapidly regulating thymic export where S1P receptor agonism alters both phenotypic maturation and egress of thymocytes into blood during late thymic maturation. The S1P system is now shown to acutely regulate both thymic and lymph node egress. Inhibition of lymphocyte egress from thymus and lymph node can contribute synergistically to clinically useful immunosupression by disrupting recirculation of peripheral T cells. [References: 66]
机译：仅选择每天在胸腺中产生的少量T细胞来补充周围的T细胞库。关于胸腺选择的知识很多。然而，对髓质成熟和成熟T细胞向血液中释放的调节机制知之甚少。在这里，我们证明了鞘氨醇胸腺细胞表型成熟的快速加速，因为鞘氨醇1-磷酸（S1P）受体激动剂引起的CD69丢失。低纳摩尔激动剂浓度选择性诱导CD69（int）CD62L（高）单阳性T细胞的变化，导致2小时内CD69的下调。当CD69丢失加速时，成熟T细胞进入血液的抑制在2小时内> 95％。两种方法均表现出平行的敏感性和剂量反应。总之，这些数据揭示了一种有效调节胸腺输出的有效手段，其中S1P受体激动作用会改变胸腺成熟后期的表型成熟和胸腺细胞向血液的流出。现在表明，S1P系统可以急性调节胸腺和淋巴结的流出。抑制胸腺和淋巴结流出的淋巴细胞可通过破坏外周T细胞的再循环而协同促进临床上有用的免疫抑制。 [参考：66]

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