CXCL12-CXCR4 engagement is required for migration of cutaneous dendritic cells
CXCL12-CXCR4 engagement is required for migration of cutaneous dendritic cells
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DOI：
10.2353/ajpath.2007.070225
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发表时间：
2007-10-01
影响因子：
6
通讯作者：
Tokura, Yoshilki
中科院分区：
文献类型：
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作者：
Kabashima, Kenji;Shiraishi, Noriko;Tokura, Yoshilki
CCR7被认为是皮肤树突状细胞(DC)向区域淋巴结迁移所必需的趋化因子受体。然而，CCR7缺陷小鼠不能获得完全的迁移抑制，这表明存在其他趋化因子受体参与这一过程。最初，我们发现CXCR4在迁移的皮肤树突状细胞上高度表达，其配体CXCL12在皮肤的Lyve-1(+)淋巴管中检测到。特异性CXCR4拮抗剂4-F-苯甲酰-TN14003可抑制FITC诱导的DC向引流淋巴结的迁移。在FITC+细胞中，CD11c(高+)CD11b(int+)细胞和CD11c(高+)CD11b(高+)+CD11c(低+)CD11b(int+)细胞分别为朗格林(+)朗格汉斯细胞和朗格林(-)(真皮)DDC亚群，两者均被CXCR4拮抗剂抑制。此外，在致敏阶段给予CXCR4拮抗剂可降低体内接触性超敏反应。CXCR4拮抗剂可抑制致敏淋巴结细胞对二硝基苯磺酸的体外增殖反应。这些结果表明，CXCL12-CXCR4结合在皮肤DC上，通过促进皮肤DC迁移，在启动皮肤免疫反应中起着至关重要的作用。
CCR7 is regarded as an essential chemokine receptor for cutaneous dendritic cell (DC) migration into the regional lymph nodes. However, complete migratory inhibition cannot be obtained in CCR7-deficient mice, suggesting that there exist other chemokine receptors involved in this process. initially, we found that CXCR4 was highly expressed on migrated cutaneous DCs and that its ligand, CXCL12, was detected in the LYVE-1(+) lymphatic vessels in the skin. FITC-induced cutaneous DC migration into the draining lymph nodes was impaired by the specific CXCR4 antagonist 4-F-Benzoyl-TN14003. Among FITC+ cells, Langerin(+) Langerhans cells and Langerin(-) (dermal) dDC subsets were detected as CD11c(high+)CD11b(int+) cells and CD11c(high+)CD11b(high+) plus CD11c(low+)CD11b(int+) cells, respectively, both of which were suppressed by CXCR4 antagonist. Moreover, in vivo contact hypersensitivity response was impaired by CXCR4 antagonist administered during the sensitization phase. The in vitro proliferative response to dinitrobenzene sulfonic acid of sensitized lymph node cells was inhibited by CXCR4 antagonist treatment. These findings demonstrated that CXCL12-CXCR4 engagement on cutaneous DCs plays a crucial role in the initiation of skin immune response by enhancing cutaneous DC migration.