Cutting edge: IFN-producing cells respond to CXCR3 ligands in the presence of CXCL12 and secrete inflammatory chemokines upon activation
Cutting edge: IFN-producing cells respond to CXCR3 ligands in the presence of CXCL12 and secrete inflammatory chemokines upon activation
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DOI：
10.4049/jimmunol.169.11.6079
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发表时间：
2002-12-01
影响因子：
4.4
通讯作者：
Colonna, M
中科院分区：
文献类型：
--
作者：
Krug, A;Uppaluri, R;Colonna, M
人类天然产生干扰素的细胞 (IPC) 在血液中循环，并聚集在高内皮细胞 (HEV) 周围慢性发炎的淋巴结中。尽管 L-选择素、CXCR4 和 CCR7 被认为是关键的 IPC 归巢介质，但 CXCR3 的作用尚不清楚，因为 IPC 在体外不响应 CXCR3 配体。在这项研究中，我们表明，小鼠和人类 IPC 在体外向 CXCR3 配体的迁移需要 CXCR4 与 CXCL12 的结合。我们还证明 CXCL12 存在于人 HEV 体内。此外，在与致病刺激相互作用后，小鼠和人类 IPC 会分泌高水平的炎症趋化因子。因此，IPC 迁移到发炎淋巴结最初可能是由 L-选择素、CXCL12 和 CXCR3 配体介导的。当遇到病原体时，CCR7 可能会进一步指导 IPC 在淋巴结内的定位，并且 IPC 分泌的炎症趋化因子可能会吸引其他 IPC，从而促进淋巴结中簇的形成。
Human natural IFN-producing cells (IPC) circulate in the blood and cluster in chronically inflamed lymph nodes around high endothelial vemiles (HEV). Although L-selectin, CXCR4, and CCR7 are recognized as critical IPC homing mediators, the role of CXCR3 is unclear, since IPC do not respond to CXCR3 ligands in vitro. In this study, we show that migration of murine and human IPC to CXCR3 ligands in vitro requires engagement of CXCR4 by CXCL12. We also demonstrate that CXCL12 is present in human HEV in vivo. Moreover, after interaction with pathogenic stimuli, murine and human IPC secrete high levels of inflammatory chemokines. Thus, IPC migration into inflamed lymph nodes may be initially mediated by L-selectin, CXCL12, and CXCR3 ligands. Upon pathogen encounter,, IPC positioning within the lymph node may be further directed by CCR7 and IPC secretion of inflammatory chemokines may attract other IPC, promoting cluster formation in lymph nodes.