Immature human dendritic cells enhance their migration through KCa3.1 channel activation
Immature human dendritic cells enhance their migration through KCa3.1 channel activation
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DOI：
10.1016/j.ceca.2016.02.008
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发表时间：
2016-04-01
期刊：
影响因子：
4
通讯作者：
Velge-Roussel, Florence
中科院分区：
文献类型：
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作者：
Crottes, David;Felix, Romain;Velge-Roussel, Florence
迁移能力对于树突状细胞（dc）向T细胞呈递抗原以诱导免疫应答至关重要。DC迁移被认为是一个钙依赖的过程，但尚未完全理解。在这里，我们报道了KCa3.1/1K1/iSK4通道在未成熟（iDC）和成熟（mDC）人类CD14（+）衍生的dc的迁移能力中的作用。KCa3.1通道被证明控制人DC的膜电位和Ca2+进入，这与迁移能力直接相关。用TRAM 34 （100 nM）修饰两种dc中迁移标志物CCR5和CCR7的表达。但是，使用TRAM-34和KCa3.1 siRNA只会减少iDC的迁移。共聚焦分析显示，在iDC稳态下，CCR5与KCa3.1紧密定位。最后，KCa3.1的影响似乎仅限于迁移能力，因为T细胞对dc的激活似乎没有改变。综上所述，这些结果表明KCa3.1通道对iDC迁移具有促迁移作用。我们的研究结果表明，KCa3.1在人类iDC的迁移中发挥了重要作用，并构成了细胞治疗优化的一个有吸引力的靶点。(C) 2016 Elsevier Ltd.版权所有。
Migration capacity is essential for dendritic cells (DCs) to present antigen to T cells for the induction of immune response. The DC migration is supposed to be a calcium-dependent process, while not fully understood. Here, we report a role of the KCa3.1/1K1/iSK4 channels in the migration capacity of both immature (iDC) and mature (mDC) human CD14(+)-derived DCs. KCa3.1 channels were shown to control the membrane potential of human DC and the Ca2+ entry, which is directly related to migration capacities. The expression of migration marker such as CCR5 and CCR7 was modified in both types of DCs by TRAM 34 (100 nM). But, only the migration of iDC was decreased by use of both TRAM-34 and KCa3.1 siRNA. Confocal analyses showed a close localization of CCR5 with KCa3.1 in the steady state of iDC. Finally, the implication of KCa3.1 seems to be limited to the migration capacities as T cell activation of DCs appeared unchanged. Altogether, these results demonstrated that KCa3.1 channels have a pro-migratory effect on iDC migration. Our findings suggest that KCa3.1 in human iDC play a major role in their migration and constitute an attractive target for the cell therapy optimization. (C) 2016 Elsevier Ltd. All rights reserved.