Type I interferon dependence of plasmacytoid dendritic cell activation and migration.

Type I interferon dependence of plasmacytoid dendritic cell activation and migration.
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DOI:
10.1084/jem.20041930
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发表时间:
2005-04-04
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Trinchieri G
Trinchieri G
中科院分区:
其他
文献类型:
--
作者:
Asselin-Paturel C;Brizard G;Chemin K;Boonstra A;O'Garra A;Vicari A;Trinchieri G

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传统树突状细胞 (cDC) 和浆细胞样 DC (pDC) 的 Toll 样受体 (TLR) 差异表达被认为影响微生物病原体诱导的免疫反应类型。在这项研究中,我们表明,在体内,cDC 和 pDC 同等地被 TLR4、-7 和 -9 配体激活。 I 型干扰素 (IFN) 对于响应所有三种 TLR 配体的体内 pDC 激活非常重要,而 cDC 仅需要 I 型 IFN 信号传导来激活 TLR9,部分激活 TLR7 介导的激活。尽管TLR配体诱导脾cDC原位迁移至T细胞区域,但注射TLR9和TLR7配体后6小时,脾pDC分别在边缘区和外部T细胞区域形成簇。 TLR9配体的体内治疗降低了pDC响应IFN诱导的CXCR3配体而离体迁移的能力,并增加了它们对CCR7配体的反应。与 cDC 不同,pDC 的迁移模式需要 I 型 IFN 来诱导 CXCR3 配体并对 CCR7 配体做出反应。这些数据表明,小鼠 pDC 在对 TLR 配体的体内反应方面与 cDC 不同,在激活和迁移的模式和 I 型 IFN 需求方面。
Differential expression of Toll-like receptor (TLR) by conventional dendritic cells (cDCs) and plasmacytoid DC (pDCs) has been suggested to influence the type of immune response induced by microbial pathogens. In this study we show that, in vivo, cDCs and pDCs are equally activated by TLR4, -7, and -9 ligands. Type I interferon (IFN) was important for pDC activation in vivo in response to all three TLR ligands, whereas cDCs required type I IFN signaling only for TLR9- and partially for TLR7-mediated activation. Although TLR ligands induced in situ migration of spleen cDC into the T cell area, spleen pDCs formed clusters in the marginal zone and in the outer T cell area 6 h after injection of TLR9 and TLR7 ligands, respectively. In vivo treatment with TLR9 ligands decreased pDC ability to migrate ex vivo in response to IFN-induced CXCR3 ligands and increased their response to CCR7 ligands. Unlike cDCs, the migration pattern of pDCs required type I IFN for induction of CXCR3 ligands and responsiveness to CCR7 ligands. These data demonstrate that mouse pDCs differ from cDCs in the in vivo response to TLR ligands, in terms of pattern and type I IFN requirement for activation and migration.
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