CCR7 mediates the migration of Foxp3+ regulatory T cells to the paracortical areas of peripheral lymph nodes through high endothelial venules
CCR7 mediates the migration of Foxp3+ regulatory T cells to the paracortical areas of peripheral lymph nodes through high endothelial venules
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DOI：
10.1189/jlb.0906574
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发表时间：
2007-11-01
影响因子：
5.5
通讯作者：
Matsushima, Kouji
中科院分区：
文献类型：
--
作者：
Ueha, Satoshi;Yoneyama, Hiroyuki;Matsushima, Kouji
胸腺衍生的叉头框 p3(+) 天然存在的调节性 T 细胞 (nTreg) 被认为在全身循环，通过与树突状细胞 (DC) 相互作用来维持外周免疫自我耐受，从而对常规 T 细胞进行调节。然而，推测参与 nTreg 体内迁移的趋化因子受体尚未完全确定。在这里，我们证明淋巴结 nTreg 在过继转移后优先迁移到淋巴结的副皮质区域，观察到它们频繁与 CD8 α(+) DC 和 CD8 α(-) CD11b(-) DC 接触。当从 CCR7 缺陷小鼠中制备细胞时，nTreg 向副皮质区域的迁移受到严重损害。然而，在某种程度上，在此类CCR7缺陷小鼠中也观察到了nTreg的不依赖于CCR7的迁移，但这主要发生在髓质高内皮微静脉中。总而言之，这些数据提供了证据，证明 CCR7 在稳态条件下介导 nTreg 迁移到淋巴结的皮质旁区域；然而，不依赖 CCR7 的迁移也发生在髓质中。
Thymus-derived forkhead box p3(+) naturally occurring regulatory T cells (nTreg) are thought to circulate throughout the body to maintain peripheral immunological self-tolerance through interactions with dendritic cells (DCs), resulting in regulation of conventional T cells. However, the chemokine receptors, which are putatively involved in the in vivo migration of nTreg, have not been fully established. Here, we demonstrated that lymph node nTreg preferentially migrated to the paracortical area of lymph nodes after adoptive transfer, where they were observed to make contact frequently with CD8 alpha(+) DCs and CD8 alpha(-) CD11b(-) DCs. This migration of nTreg to the paracortical areas was impaired severely when cells were prepared from CCR7-deficient mice. However, to some extent, CCR7-independent migration of nTreg in such CCR7-deficient mice was also observed, but this occurred mainly in the medullary high endothelial venules. Taken together, these data provide the evidence that CCR7 mediates nTreg migration to the paracortical areas of lymph nodes under steady-state conditions; however, CCR7-independent migration also takes place in the medulla.