External antigen uptake by Langerhans cells with reorganization of epidermal tight junction barriers.

External antigen uptake by Langerhans cells with reorganization of epidermal tight junction barriers.
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DOI:
10.1084/jem.20091527
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发表时间:
2009-12-21
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Amagai M
Amagai M
中科院分区:
其他
文献类型:
--
作者:
Kubo A;Nagao K;Yokouchi M;Sasaki H;Amagai M

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最外层的屏障对于陆生动物避免干燥和保护身体免受外来伤害至关重要。哺乳动物的皮肤由两组屏障组成:角质层(SC)和紧密连接(TJs)。尽管存在这些障碍,表皮朗格汉斯细胞(LCs)如何获得外部抗原(Ags)仍是未知的。我们发现,激活诱导的LCs延长其树突以穿透角化细胞(KC) TJ,并调查位于TJ屏障外的TJ外环境,就在SC下方。穿透的树突从Ags与langerin/Birbeck颗粒共定位的尖端摄取Ags。KC-KC接触处的TJs通过在LC - kc接触处动态形成新的依赖于cludin的双细胞和三细胞依赖的三细胞TJs,允许LC树突穿透,从而在银摄取过程中保持TJ的完整性。因此,在角化的SC屏障下,LCs和KCs表现出显著的合作,使LCs能够进入违反SC屏障的外部ag,同时保留TJ屏障以保护TJ内部环境。
Outermost barriers are critical for terrestrial animals to avoid desiccation and to protect their bodies from foreign insults. Mammalian skin consists of two sets of barriers: stratum corneum (SC) and tight junctions (TJs). How acquisition of external antigens (Ags) by epidermal Langerhans cells (LCs) occur despite these barriers has remained unknown. We show that activation-induced LCs elongate their dendrites to penetrate keratinocyte (KC) TJs and survey the extra-TJ environment located outside of the TJ barrier, just beneath the SC. Penetrated dendrites uptake Ags from the tip where Ags colocalize with langerin/Birbeck granules. TJs at KC–KC contacts allow penetration of LC dendrites by dynamically forming new claudin-dependent bicellular- and tricellulin-dependent tricellular TJs at LC–KC contacts, thereby maintaining TJ integrity during Ag uptake. Thus, covertly under keratinized SC barriers, LCs and KCs demonstrate remarkable cooperation that enables LCs to gain access to external Ags that have violated the SC barrier while concomitantly retaining TJ barriers to protect intra-TJ environment.
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