C-C chemokine receptor 6-regulated entry of TH-17 cells into the CNS through the choroid plexus is required for the initiation of EAE
C-C chemokine receptor 6-regulated entry of TH-17 cells into the CNS through the choroid plexus is required for the initiation of EAE
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DOI：
10.1038/ni.1716
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发表时间：
2009-05-01
影响因子：
30.5
通讯作者：
Sallusto, Federica
中科院分区：
文献类型：
--
作者：
Reboldi, Andrea;Coisne, Caroline;Sallusto, Federica
产生白细胞介素17的T辅助细胞（TH-17细胞）在实验性自身免疫性脑脊髓炎中是重要的，但它们进入中枢神经系统（CNS）的途径及其相对于其他效应T细胞的贡献仍有待确定。在这里，我们发现缺乏CCR 6（TH-17细胞特有的趋化因子受体）的小鼠会产生TH-17反应，但对实验性自身免疫性脑脊髓炎的诱导具有高度抵抗力。疾病易感性通过转移野生型T细胞重建，所述野生型T细胞在疾病发作前进入CNS并触发效应T细胞在活化的实质血管中的大量CCR 6非依赖性募集。CCR 6配体CCL 20在小鼠和人的脉络丛上皮细胞中组成型表达。我们的结果确定了淋巴细胞进入未炎症与炎症中枢神经系统的不同分子要求和端口，并表明脉络丛中的CCR 6-CCL 20轴控制着中枢神经系统的免疫监视。
Interleukin 17-producing T helper cells (TH-17 cells) are important in experimental autoimmune encephalomyelitis, but their route of entry into the central nervous system (CNS) and their contribution relative to that of other effector T cells remain to be determined. Here we found that mice lacking CCR6, a chemokine receptor characteristic of TH-17 cells, developed TH-17 responses but were highly resistant to the induction of experimental autoimmune encephalomyelitis. Disease susceptibility was reconstituted by transfer of wild-type T cells that entered into the CNS before disease onset and triggered massive CCR6-independent recruitment of effector T cells across activated parenchymal vessels. The CCR6 ligand CCL20 was constitutively expressed in epithelial cells of choroid plexus in mice and humans. Our results identify distinct molecular requirements and ports of lymphocyte entry into uninflamed versus inflamed CNS and suggest that the CCR6-CCL20 axis in the choroid plexus controls immune surveillance of the CNS.