Selective recruitment of immature and mature dendritic cells by distinct chemokines expressed in different anatomic sites.
Selective recruitment of immature and mature dendritic cells by distinct chemokines expressed in different anatomic sites.
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DOI：
10.1084/jem.188.2.373
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发表时间：
1998-07-20
影响因子：
15.3
通讯作者：
Caux, C
中科院分区：
文献类型：
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作者：
Dieu, M C;Vanbervliet, B;Vicari, A;Bridon, J M;Oldham, E;Ait-Yahia, S;Briere, F;Zlotnik, A;Lebecque, S;Caux, C
DC（树突状细胞）充当免疫系统的哨兵。它们从血液运输到组织，虽然不成熟，但它们捕获抗原。然后它们离开组织并移动到引流淋巴器官，在那里转化为成熟的 DC，启动幼稚 T 细胞。 DC交通模式和功能之间的这种暗示性联系促使我们研究DC在其发育和成熟过程中的趋化因子反应性。 DC 可以从用粒细胞/巨噬细胞集落刺激因子 (GM-CSF) 加肿瘤坏死因子 (TNF)-α 培养的 CD34+ 造血祖细胞 (HPC) 分化，也可以从用 GM-CSF 加白细胞介素 4 培养的单核细胞分化。源自 CD34+ HPC 的未成熟 DC 在响应 巨噬细胞炎症蛋白 (MIP)-3α，还包括 MIP-1α 和 RANTES（调节激活、正常 T 细胞表达和分泌）。成熟后，在 TNF-α、脂多糖或 CD40L 的诱导下，DC 在获得对单一其他趋化因子 MIP-3β 的持续反应性时，就会失去对这三种趋化因子的反应。 CC 趋化因子受体 (CCR)6 和 CCR7 分别是 MIP-3α 和 MIP-3β 唯一已知的受体。随着 DC 成熟，CCR6 mRNA 表达逐渐降低，而 CCR7 mRNA 表达急剧上调，这一观察结果为趋化因子反应性的变化提供了可能的解释。类似地，MIP-3β 反应性和 CCR7 表达在单核细胞衍生的 DC 成熟时被诱导。此外，自发成熟后从血液中分离的 CD11c+ DC 也获得了对 MIP-3β 的趋化反应。最后，通过原位杂交检测仅在扁桃体发炎的上皮隐窝内的MIP-3α mRNA，以及特异地在富含T细胞的区域中的MIP-3β mRNA，表明MIP-3α/CCR6在损伤部位募集未成熟DC中的作用以及MIP-3β/CCR7在富含T细胞的区域中负载抗原的成熟DC的积累中发挥作用。
DCs (dendritic cells) function as sentinels of the immune system. They traffic from the blood to the tissues where, while immature, they capture antigens. They then leave the tissues and move to the draining lymphoid organs where, converted into mature DC, they prime naive T cells. This suggestive link between DC traffic pattern and functions led us to investigate the chemokine responsiveness of DCs during their development and maturation. DCs were differentiated either from CD34+ hematopoietic progenitor cells (HPCs) cultured with granulocyte/macrophage colony–stimulating factor (GM-CSF) plus tumor necrosis factor (TNF)-α or from monocytes cultured with GM-CSF plus interleukin 4. Immature DCs derived from CD34+ HPCs migrate most vigorously in response to macrophage inflammatory protein (MIP)-3α, but also to MIP-1α and RANTES (regulated on activation, normal T cell expressed and secreted). Upon maturation, induced by either TNF-α, lipopolysaccharide, or CD40L, DCs lose their response to these three chemokines when they acquire a sustained responsiveness to a single other chemokine, MIP-3β. CC chemokine receptor (CCR)6 and CCR7 are the only known receptors for MIP-3α and MIP-3β, respectively. The observation that CCR6 mRNA expression decreases progressively as DCs mature, whereas CCR7 mRNA expression is sharply upregulated, provides a likely explanation for the changes in chemokine responsiveness. Similarly, MIP-3β responsiveness and CCR7 expression are induced upon maturation of monocyte- derived DCs. Furthermore, the chemotactic response to MIP-3β is also acquired by CD11c+ DCs isolated from blood after spontaneous maturation. Finally, detection by in situ hybridization of MIP-3α mRNA only within inflamed epithelial crypts of tonsils, and of MIP-3β mRNA specifically in T cell–rich areas, suggests a role for MIP-3α/CCR6 in recruitment of immature DCs at site of injury and for MIP-3β/CCR7 in accumulation of antigen-loaded mature DCs in T cell–rich areas.