Functional tight junction barrier localizes in the second layer of the stratum granulosum of human epidermis
Functional tight junction barrier localizes in the second layer of the stratum granulosum of human epidermis
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DOI：
10.1016/j.jdermsci.2013.04.021
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发表时间：
2013-08-01
影响因子：
4.6
通讯作者：
Kubo, Akiharu
中科院分区：
文献类型：
--
作者：
Yoshida, Kazue;Yokouchi, Mariko;Kubo, Akiharu
背景：哺乳动物表皮有两个扩散屏障，角质层（SC）和紧密连接（TJ）。我们以前曾报道过在小鼠的SC和形成TJ的角质形成细胞之间存在一个单一的活细胞层，然而，TJ屏障在人表皮中的确切位置尚未确定。目的：研究表皮TJ与各种细胞-细胞连接蛋白和SC的精确分布，阐明Tis对人皮肤中大分子的屏障功能。方法：各种连接蛋白的本地化进行了研究，在人体皮肤切片和在屋顶的大疱形成的体外剥脱毒素（ET）治疗的三维。结果：人颗粒层（SG）细胞的TJ、粘附连接和桥粒蛋白在细胞的最上层（SG1-SG3）有明显的分布。ET或scEv的离体注射证明，只有SG2-SG2连接作为TJ屏障起作用，限制了这些蛋白质的由内向外扩散。由离体ET治疗形成的大疱的屋顶由SC，SG1细胞，和TJ形成SG2细胞，可能模仿大疱形成在bullous impelment.Conclusion：人表皮有三个SG细胞层，具有不同的属性，下面的SC，其中只有SG2细胞具有功能性TJ。我们的研究结果表明，SG2细胞之间的人表皮Tjs形成对可溶性蛋白质，包括免疫球蛋白和细菌毒素的细胞旁扩散屏障。(C)2013年日本皮肤病研究学会。由Elsevier爱尔兰有限公司出版。保留所有权利。
Background: Mammalian epidermis has two diffusion barriers, the stratum corneum (SC) and tight junctions (TJs). We reported previously that a single living cell layer exists between the SC and TJ-forming keratinocytes in mice; however, the exact location of the TJ barrier in human epidermis has not been defined.Objective: To investigate the precise distribution of epidermal TJs in relation to various cell-cell junction proteins and the SC and to clarify the barrier function of Tis against macromolecules in human skin.Methods: The localization of various junctional proteins was investigated in human skin sections and in the roofs of bullae formed by ex vivo exfoliative toxin (ET) treatment in three dimensions. ET and single-chain variable fragments (scFv) against desmoglein 1 were used as large diffusion probes.Results: Human stratum granulosum (SG) cells have a distinct distribution of TJ, adherens junction, and desmosome proteins in the uppermost three layers (SG1-SG3 from the surface inward). Ex vivo injection of ET or scEv demonstrated that only SG2-SG2 junctions function as a TJ barrier, limiting the inside-out diffusion of these proteins. The roofs of bullae formed by ex vivo ET treatment consisted of SC, SG1 cells, and TJ-forming SG2 cells, probably mimicking bulla formation in bullous impetigo.Conclusion: Human epidermis has three SG cell layers with distinct properties just beneath the SC, of which only SG2 cells have functional TJs. Our results suggest that human epidermal Tjs between SG2 cells form a paracellular diffusion barrier against soluble proteins, including immunoglobulins and bacterial toxins. (C) 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.