癌症相关上皮细胞粘附分子 (EpCAM; CD326) 使表皮朗格汉斯细胞能够在体内运动和迁移。,Proceedings of the National Academy of Sciences of the United States of America

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癌症相关上皮细胞粘附分子 (EpCAM; CD326) 使表皮朗格汉斯细胞能够在体内运动和迁移。
Proceedings of the National Academy of Sciences of the United States of America ( IF 9.4 ) Pub Date : 2012 Apr 10 , DOI: 10.1073/pnas.1117674109
Maria R Gaiser ₁ , Tim Lämmermann , Xu Feng , Botond Z Igyarto , Daniel H Kaplan , Lino Tessarollo , Ronald N Germain , Mark C Udey

Affiliation

激活后，朗格汉斯细胞 (LC)，一种独特的表皮驻留树突状细胞亚群，从皮肤迁移到淋巴结，在那里它们调节由表皮应用抗原引发的免疫反应的大小和质量。LC-角质形成细胞粘附的调节可能是调节 LC 迁移的核心。LC 表达高水平的上皮细胞粘附分子 (EpCAM；CD326)，这是一种细胞表面蛋白，是某些上皮细胞和许多癌的特征，并且与细胞间粘附和转移有关。为了深入了解体内生理环境中的 EpCAM 功能，我们生成了具有 EpCAM 缺陷型 LC 的条件敲除小鼠并对其进行了表征。这些小鼠的表皮含有增加的 LC 数量，同时具有正常水平的 MHC 和共刺激分子以及体外 T 细胞刺激活性。EpCAM 缺陷型 LC 从皮肤外植体的迁移受到抑制，但解离 LC 的趋化性不受抑制。相应地，接触过敏原刺激的、缺乏 EpCAM 的 LC 在体内退出表皮的能力被延迟，并且随后在淋巴结中积累的带有半抗原的 LC 显着减少。EpCAM 缺陷型 LC 的迁移减弱导致接触性超敏反应增强，如先前在 LC 缺陷型小鼠中所述。活体显微镜检查显示，接触过敏原处理的小鼠体内 EpCAM 缺陷型 LC 的易位和树突运动性降低。这些结果最终将 EpCAM 表达与 LC 运动/迁移和 LC 迁移与免疫调节联系起来。

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Cancer-associated epithelial cell adhesion molecule (EpCAM; CD326) enables epidermal Langerhans cell motility and migration in vivo.

After activation, Langerhans cells (LC), a distinct subpopulation of epidermis-resident dendritic cells, migrate from skin to lymph nodes where they regulate the magnitude and quality of immune responses initiated by epicutaneously applied antigens. Modulation of LC-keratinocyte adhesion is likely to be central to regulation of LC migration. LC express high levels of epithelial cell adhesion molecule (EpCAM; CD326), a cell-surface protein that is characteristic of some epithelia and many carcinomas and that has been implicated in intercellular adhesion and metastasis. To gain insight into EpCAM function in a physiologic context in vivo, we generated conditional knockout mice with EpCAM-deficient LC and characterized them. Epidermis from these mice contained increased numbers of LC with normal levels of MHC and costimulatory molecules and T-cell-stimulatory activity in vitro. Migration of EpCAM-deficient LC from skin explants was inhibited, but chemotaxis of dissociated LC was not. Correspondingly, the ability of contact allergen-stimulated, EpCAM-deficient LC to exit epidermis in vivo was delayed, and strikingly fewer hapten-bearing LC subsequently accumulated in lymph nodes. Attenuated migration of EpCAM-deficient LC resulted in enhanced contact hypersensitivity responses as previously described in LC-deficient mice. Intravital microscopy revealed reduced translocation and dendrite motility in EpCAM-deficient LC in vivo in contact allergen-treated mice. These results conclusively link EpCAM expression to LC motility/migration and LC migration to immune regulation. EpCAM appears to promote LC migration from epidermis by decreasing LC-keratinocyte adhesion and may modulate intercellular adhesion and cell movement within in epithelia during development and carcinogenesis in an analogous fashion.

更新日期：2017-01-31

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