CCR7 defines a precursor for murine iNKT cells in thymus and periphery.
CCR7 defines a precursor for murine iNKT cells in thymus and periphery.
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DOI：
10.7554/elife.34793
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发表时间：
2018-08-13
期刊：
影响因子：
7.7
通讯作者：
Hogquist KA
中科院分区：
文献类型：
--
作者：
Wang H;Hogquist KA
胸腺和外周iNKT亚群分化的确切步骤一直存在争议。我们在这里证明了一小部分胸腺iNKT和粘膜相关的表达CCR7的不变T细胞代表了一个多能祖细胞库，在胸腺内产生效应亚群。通过胸腺内标记，我们还发现CCR7+ iNKT细胞以Klf2依赖的方式从胸腺迁移，并在到达外周后进一步成熟。Ccr7缺陷损害了iNKT效应亚群的分化和向髓质的定位。异种共生和胸腺内转移表明胸腺NKT1和NKT17是常驻的——它们不是来自外周池，也不参与外周池。最后，每个胸腺iNKT效应亚群产生不同的影响T细胞发育的因子。我们的研究结果表明，胸腺既是iNKT祖细胞的来源，也是组织依赖性效应细胞分化的独特位点。
The precise steps of iNKT subset differentiation in the thymus and periphery have been controversial. We demonstrate here that the small proportion of thymic iNKT and mucosal associated invariant T cells that express CCR7 represent a multi-potent progenitor pool that gives rise to effector subsets within the thymus. Using intra-thymic labeling, we also showed that CCR7+ iNKT cells emigrate from the thymus in a Klf2 dependent manner, and undergo further maturation after reaching the periphery. Ccr7 deficiency impaired differentiation of iNKT effector subsets and localization to the medulla. Parabiosis and intra-thymic transfer showed that thymic NKT1 and NKT17 were resident—they were not derived from and did not contribute to the peripheral pool. Finally, each thymic iNKT effector subset produces distinct factors that influence T cell development. Our findings demonstrate how the thymus is both a source of iNKT progenitors and a unique site of tissue dependent effector cell differentiation.