Innate control of actin nucleation determines two distinct migration behaviours in dendritic cells.

Innate control of actin nucleation determines two distinct migration behaviours in dendritic cells.
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DOI:
10.1038/ncb3284
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发表时间:
2016-01
影响因子:
21.3
通讯作者:
Lennon-Duménil AM
Lennon-Duménil AM
中科院分区:
生物学1区
文献类型:
--
作者:
Vargas P;Maiuri P;Bretou M;Sáez PJ;Pierobon P;Maurin M;Chabaud M;Lankar D;Obino D;Terriac E;Raab M;Thiam HR;Brocker T;Kitchen-Goosen SM;Alberts AS;Sunareni P;Xia S;Li R;Voituriez R;Piel M;Lennon-Duménil AM

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树突状细胞(DC)在外周组织中的迁移有两个主要功能:未成熟DC的抗原采样和趋化因子引导的成熟后向淋巴管(LV)的迁移。这些迁移事件决定了适应性免疫应答的效率。它们受核心细胞运动机制的调节尚未确定。在这里,我们表明,未成熟的树突状细胞的迁移取决于两个主要的肌动蛋白池:RhoA-mDia 1依赖的肌动蛋白池位于其后方,这有利于向前运动;和Cdc 42-Arp 2/3依赖的肌动蛋白池存在于其前面,这限制了迁移,但促进抗原捕获。在TLR 4-MyD 88诱导的成熟后,Arp 2/3依赖的肌动蛋白在细胞前端的富集显著减少。因此,成熟的DC切换到更快和更持久的mDia 1依赖性运动模式,促进趋化性迁移到LV和淋巴结。因此,肌动蛋白成核机制的差异化使用根据其特定功能优化了未成熟和成熟DC的迁移。
Dendritic cell (DC) migration in peripheral tissues serves two main functions: antigen sampling by immature DCs, and chemokine-guided migration towards lymphatic vessels (LVs) on maturation. These migratory events determine the efficiency of the adaptive immune response. Their regulation by the core cell locomotion machinery has not been determined. Here, we show that the migration of immature DCs depends on two main actin pools: a RhoA–mDia1-dependent actin pool located at their rear, which facilitates forward locomotion; and a Cdc42–Arp2/3-dependent actin pool present at their front, which limits migration but promotes antigen capture. Following TLR4–MyD88-induced maturation, Arp2/3-dependent actin enrichment at the cell front is markedly reduced. Consequently, mature DCs switch to a faster and more persistent mDia1-dependent locomotion mode that facilitates chemotactic migration to LVs and lymph nodes. Thus, the differential use of actin-nucleating machineries optimizes the migration of immature and mature DCs according to their specific function.
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