CCL19/CCL21-triggered signal transduction and migration of dendritic cells requires prostaglandin E2
CCL19/CCL21-triggered signal transduction and migration of dendritic cells requires prostaglandin E2
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DOI：
10.1182/blood-2003-05-1643
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发表时间：
2004-03-01
期刊：
影响因子：
20.3
通讯作者：
Groettrup, M
中科院分区：
文献类型：
--
作者：
Scandella, E;Men, Y;Groettrup, M
树突状细胞（DC）迁移的控制是启动细胞免疫应答的关键。当被炎症刺激物激活时，趋化因子受体CCR 7在DC上上调。活化的DC归巢于淋巴器官，其中CCR 7配体CCL 19和。CCL 21表达。我们先前发现，人单核细胞衍生的DC（MoDC）在前列腺素（PG）E2存在下成熟时仅迁移到CCL 19和CCL 21。由于PGE 2不改变CCR 7细胞表面的表达，我们研究了PGE 2是否可能通过将CCR 7与信号转导模块偶联来发挥其作用。事实上，当MoDCs在PGE 2存在下成熟时，用CCR 7配体刺激导致增强的磷脂酰肌醇-3-激酶介导的蛋白激酶B磷酸化。此外，CCL 19/CCL 21诱导的MoDC细胞内钙动员仅在成熟过程中存在PGE 2时发生。MoDC向CCL 19和CCL 21的迁移依赖于磷脂酶C和细胞内钙流，但不依赖于磷脂酰肌醇-3激酶。因此，我们的数据提供了对CCL 19/CCL 21触发的信号转导通路的深入了解，并确定了PGE 2通过促进CCR 7信号转导来控制成熟MoDC迁移的新功能。(C)2004年，美国血液学会。
The control of dendritic cell (DC) migration is pivotal for the initiation of cellular immune responses. When activated with inflammatory stimuli, the chemokine receptor CCR7 is up-regulated on DCs. Activated DCs home to lymphoid organs, where the CCR7 ligands CCL19 and. CCL21 are expressed. We previously found that human monocyte-derived DCs (MoDCs) exclusively migrated to CCL19 and CCL21 when matured in the presence of prostaglandin (PG) E2. Because PGE2 did not alter CCR7 cell surface expression, we examined whether PGE2 may exert its effect by coupling CCR7 to signal transduction modules. Indeed, stimulation with CCR7 ligands led to enhanced phosphatidylinositol-3-kinase-mediated phosphorylation of protein kinase B when MoDCs were matured in the presence of PGE2. Moreover, CCL19/CCL21-induced intracellular calcium mobilization in MoDCs occurred only when PGE2 was present during maturation. MoDC migration to CCL19 and CCL21 was dependent on phospholipase C and intracellular calcium flux but not on phosphatidylinositol-3 kinase. Hence, our data provide insight into CCL19/CCL21-triggered signal transduction pathways and identify a novel function for PGE2 in controlling the migration of mature MoDCs by facilitating CCR7 signal transduction. (C) 2004 by The American Society of Hematology.